Detailed description page of ThPDB2
| This page displays user query in tabular form. |
Th1249 details |
| Primary information | |
|---|---|
| ID | 11447 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Agents Causing Muscle Toxicity |
| Patents Number | 5288703 |
| Date of Issue | 22-02-1994 |
| Date of Expiry | 07-10-2011 |
| Drug Interaction | Cilostazol,Prednisone,Diethylstilbestrol,Chlorotrianisene,Conjugated estrogens,Estradiol,Ethinylestradiol,Mestranol,Estrone sulfate,Quinestrol,Hexestrol,Tibolone,Synthetic Conjugated Estrogens, A,Synthetic Conjugated Estrogens, B,Polyestradiol phosphate,Esterified estrogens,Zeranol,Equol,Methallenestril,Epimestrol,Moxestrol,Estradiol acetate,Estradiol valerate,Biochanin A,Formononetin,Estriol,Estetrol,Cortisone acetate,Leuprolide,Infliximab,Daptomycin,Cyclosporine,Pravastatin,Baclofen,Sildenafil,Indinavir,Lovastatin,Cladribine,Phenytoin,Pamidronic acid,Mefloquine,Tacrine,Carbimazole,Cerivastatin,Trimethoprim,Montelukast,Zidovudine,Cimetidine,Ritonavir,Lercanidipine,Ciprofloxacin,Vincristine,Propylthiouracil,Methotrexate,Enalapril,Nizatidine,Ivermectin,Chloroquine,Niacin,Alendronic acid,Clofibrate,Simvastatin,Stavudine,Nafarelin,Amphotericin B,Mycophenolate mofetil,Naltrexone,Lamivudine,Ibandronate,Propofol,Terbinafine,Penicillamine,Ranitidine,Tacrolimus,Eprosartan,Risedronic acid,Bumetanide,Triazolam,Ethanol,Salmeterol,Isoniazid,Methyldopa,Isotretinoin,Cytarabine,Ganciclovir,Letrozole,Minocycline,Procainamide,Fenofibrate,Norfloxacin,Atorvastatin,Iloprost,Fluvastatin,Leflunomide,Rosuvastatin,Amiodarone,Ofloxacin,Procarbazine,Captopril,Paclitaxel,Saquinavir,Metoclopramide,Dexamethasone,Gemfibrozil,Docetaxel,Bezafibrate,Colchicine,Fusidic acid,Trabectedin,Mevastatin,Raltegravir,Pitavastatin,Etofibrate,Acipimox,Ciprofibrate,Ubidecarenone,Tianeptine,Mebeverine,Ipecac,Emetine,Simfibrate,Ronifibrate,Aluminium clofibrate,Clofibride,Fenofibric acid,Fluvoxamine,Bortezomib,Betaxolol,Caffeine,Carmustine,Lidocaine,Ropivacaine,Penciclovir,Zolmitriptan,Acetaminophen,Amitriptyline,Olanzapine,Chlorzoxazone,Clozapine,Grepafloxacin,Mirtazapine,Mexiletine,Triamterene,Promazine,Zolpidem,Entecavir,Nabumetone,Fluoxetine,Chlorpromazine,Flutamide,Haloperidol,Albendazole,Mephenytoin,Rofecoxib,Cinnarizine,Fenfluramine,Diclofenac,Imatinib,Efavirenz,Guanabenz,Pemetrexed,Verapamil,Paroxetine,Thiabendazole,Riluzole,Zileuton,Clopidogrel,Mefenamic acid,Acyclovir,Naproxen,Pentoxifylline,Trifluoperazine,Perphenazine,Ondansetron,Cyclobenzaprine,Maprotiline,Alosetron,Azelastine,Lomefloxacin,Ramelteon,Azathioprine,Frovatriptan,Levobupivacaine,Cinacalcet,Selegiline,Tocainide,Praziquantel,Melatonin,Primaquine,Hesperetin,Nifedipine,Carvedilol,Doxepin,Propafenone,Domperidone,Dexfenfluramine,Flecainide,Oxtriphylline,Rasagiline,Temafloxacin,Theobromine,Aminophenazone,Fenethylline,Bromazepam,Thiothixene,Etoricoxib,Genistein,8-azaguanine,Xanthine,9-Methylguanine,Peldesine,Phenacetin,Hypoxanthine,9-Deazaguanine,Flunarizine,Lorcaserin,Bicifadine,Lofexidine,Pirfenidone,Apremilast,GTS-21,Mianserin,Eltrombopag,Asenapine,Vadimezan,Propentofylline,Pazopanib,Agomelatine,Benzyl alcohol,Capsaicin,(R)-warfarin,Perampanel,Tasimelteon,Stiripentol,Zotepine,Methylene blue,Doxofylline,Propacetamol,Ramosetron,Selumetinib,Istradefylline,6-O-benzylguanine,Binimetinib,Voxilaprevir,Triclabendazole,Rucaparib,Lisofylline,Lobucavir,Cafedrine,Theodrenaline,Dihydralazine,Bamifylline,Proxyphylline,Acefylline,Etamiphylline,Pentifylline,Bufylline,Estradiol benzoate,Estradiol cypionate,Estradiol dienanthate,Bromotheophylline,8-chlorotheophylline,Benzocaine,Anagrelide,Theophylline,Sorafenib,Imipramine,Erlotinib,Fluorouracil,Clonidine,Tamoxifen,Warfarin,Tizanidine,Etoposide,Dacarbazine,Pimozide,Aminophylline,Clomipramine,Dasatinib,Acenocoumarol,Axitinib,Bendamustine,Pomalidomide,Tegafur,Enasidenib,Ropinirole,Macimorelin,Propranolol,Betamethasone,Triamcinolone,Medrysone,Fluorometholone,Beclomethasone dipropionate,Rimexolone,Paramethasone,Ciclesonide,Fluticasone furoate,Fluprednidene,Meprednisone,Dexamethasone isonicotinate,Deflazacort,Cortivazol,Prednylidene,Cloprednol,Fluticasone,Mometasone furoate,Prednisolone phosphate,Prednisolone hemisuccinate,Methylprednisolone hemisuccinate,Prednisone acetate,Clocortolone acetate,Melengestrol acetate,Betamethasone phosphate,Cortisone,Clobetasol propionate,Fluocinonide,Mometasone,Fluocortolone,Difluocortolone,Antipyrine,Estrone,Sulfamethoxazole,Disopyramide,Quinine,Dapagliflozin,Insulin human,Insulin lispro,Insulin glargine,Insulin pork,Troglitazone,Glimepiride,Sulfisoxazole,Acarbose,Metformin,Sulfadiazine,Rosiglitazone,Acetohexamide,Miglitol,Chlorpropamide,Nateglinide,Pentamidine,Mifepristone,Tolazamide,Repaglinide,Phenformin,Glyburide,Glipizide,Gliclazide,Tolbutamide,Pioglitazone,Bromocriptine,Gliquidone,Mitiglinide,Sitagliptin,Sunitinib,Exenatide,Mecasermin,Pramlintide,Glisoxepide,Insulin aspart,Insulin detemir,Insulin glulisine,Glymidine,AICA ribonucleotide,Buformin,Vildagliptin,Voglibose,NN344,AMG-222,Bisegliptin,Alogliptin,Saxagliptin,Liraglutide,Gosogliptin,Linagliptin,Canagliflozin,Glibornuride,Benfluorex,Empagliflozin,Albiglutide,Dulaglutide,Lobeglitazone,Netoglitazone,Rivoglitazone,Ciglitazone,Lixisenatide,Insulin beef,Insulin degludec,Insulin peglispro,Insulin tregopil,Ipragliflozin,Dutogliptin,Allicin,Tofogliflozin,Ertugliflozin,2,4-thiazolidinedione,Teneligliptin,Omarigliptin,Carmegliptin,Gemigliptin,Anagliptin,Evogliptin,Sotagliflozin,Balaglitazone,Remogliflozin etabonate,Carbutamide,Guar gum,Metahexamide,Semaglutide,Taspoglutide,Englitazone,Tirzepatide,Gastric inhibitory polypeptide,Belzutifan,Fexinidazole,Fluticasone propionate |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Bio-tropin |
| Company | Novopharm Limited |
| Brand Description | Novopharm Limited |
| Prescribed For | Subcutaneous |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11448 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Amino Acids, Peptides, and Proteins |
| Patents Number | 2252535 |
| Date of Issue | 23-06-2009 |
| Date of Expiry | 24-04-2017 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Physicians Total Care, Inc. |
| Brand Description | Physicians Total Care, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 0.2 mg/0.25mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11449 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Anterior Pituitary Lobe Hormones and Analogues |
| Patents Number | 1326439 |
| Date of Issue | 25-01-1994 |
| Date of Expiry | 25-01-2011 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Physicians Total Care, Inc. |
| Brand Description | Physicians Total Care, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 0.4 mg/0.25mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11450 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Cytochrome P-450 CYP1A2 Inducers |
| Patents Number | 6152897 |
| Date of Issue | 28-11-2000 |
| Date of Expiry | 20-11-2018 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Physicians Total Care, Inc. |
| Brand Description | Physicians Total Care, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 0.6 mg/0.25mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11451 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Cytochrome P-450 CYP1A2 Inducers (strength unknown) |
| Patents Number | 5898030 |
| Date of Issue | 27-04-1999 |
| Date of Expiry | 27-04-2016 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Physicians Total Care, Inc. |
| Brand Description | Physicians Total Care, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 0.8 mg/0.25mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11452 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Cytochrome P-450 CYP2C19 Inhibitors |
| Patents Number | 8672898 |
| Date of Issue | 18-03-2014 |
| Date of Expiry | 02-07-2022 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pharmacia and Upjohn Company LLC |
| Brand Description | Pharmacia and Upjohn Company LLC |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg/1mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11453 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Cytochrome P-450 CYP2C19 inhibitors (strength unknown) |
| Patents Number | 8684969 |
| Date of Issue | 01-04-2014 |
| Date of Expiry | 20-04-2026 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pharmacia and Upjohn Company LLC |
| Brand Description | Pharmacia and Upjohn Company LLC |
| Prescribed For | Subcutaneous |
| Chemical Name | 12 mg/1mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11454 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Cytochrome P-450 CYP2C19 Inhibitors (weak) |
| Patents Number | 9132239 |
| Date of Issue | 15-09-2015 |
| Date of Expiry | 01-08-2032 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pharmacia and Upjohn Company LLC |
| Brand Description | Pharmacia and Upjohn Company LLC |
| Prescribed For | Subcutaneous |
| Chemical Name | 0.2 mg/0.25mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11455 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Cytochrome P-450 Enzyme Inducers |
| Patents Number | 8920383 |
| Date of Issue | 30-12-2014 |
| Date of Expiry | 17-01-2027 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pharmacia and Upjohn Company LLC |
| Brand Description | Pharmacia and Upjohn Company LLC |
| Prescribed For | Subcutaneous |
| Chemical Name | 0.4 mg/0.25mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11456 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Cytochrome P-450 Enzyme Inhibitors |
| Patents Number | 7686786 |
| Date of Issue | 30-03-2010 |
| Date of Expiry | 03-08-2026 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pharmacia and Upjohn Company LLC |
| Brand Description | Pharmacia and Upjohn Company LLC |
| Prescribed For | Subcutaneous |
| Chemical Name | 0.6 mg/0.25mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11457 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Growth Hormone |
| Patents Number | 6899699 |
| Date of Issue | 31-05-2005 |
| Date of Expiry | 01-07-2022 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pharmacia and Upjohn Company LLC |
| Brand Description | Pharmacia and Upjohn Company LLC |
| Prescribed For | Subcutaneous |
| Chemical Name | 0.8 mg/0.25mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11458 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Growth Hormone, antagonists & inhibitors |
| Patents Number | 9108002 |
| Date of Issue | 18-08-2015 |
| Date of Expiry | 26-07-2026 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pharmacia and Upjohn Company LLC |
| Brand Description | Pharmacia and Upjohn Company LLC |
| Prescribed For | Subcutaneous |
| Chemical Name | 1 mg/0.25mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11459 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Hormones |
| Patents Number | RE41956 |
| Date of Issue | 23-11-2010 |
| Date of Expiry | 21-07-2021 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pharmacia and Upjohn Company LLC |
| Brand Description | Pharmacia and Upjohn Company LLC |
| Prescribed For | Subcutaneous |
| Chemical Name | 1.2 mg/0.25mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11460 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Hormones, Hormone Substitutes, and Hormone Antagonists |
| Patents Number | 6004297 |
| Date of Issue | 21-12-1999 |
| Date of Expiry | 28-07-2019 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pharmacia and Upjohn Company LLC |
| Brand Description | Pharmacia and Upjohn Company LLC |
| Prescribed For | Subcutaneous |
| Chemical Name | 1.4 mg/0.25mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11461 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Human Growth Hormone, antagonists & inhibitors |
| Patents Number | RE43834 |
| Date of Issue | 27-11-2012 |
| Date of Expiry | 28-01-2019 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pharmacia and Upjohn Company LLC |
| Brand Description | Pharmacia and Upjohn Company LLC |
| Prescribed For | Subcutaneous |
| Chemical Name | 1.6 mg/0.25mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11462 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | P-glycoprotein substrates |
| Patents Number | 5849700 |
| Date of Issue | 15-12-1998 |
| Date of Expiry | 15-12-2015 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pharmacia and Upjohn Company LLC |
| Brand Description | Pharmacia and Upjohn Company LLC |
| Prescribed For | Subcutaneous |
| Chemical Name | 1.8 mg/0.25mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11463 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Peptide Hormones |
| Patents Number | 5849704 |
| Date of Issue | 15-12-1998 |
| Date of Expiry | 15-12-2015 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pharmacia and Upjohn Company LLC |
| Brand Description | Pharmacia and Upjohn Company LLC |
| Prescribed For | Subcutaneous |
| Chemical Name | 2 mg/0.25mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11464 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Peptides |
| Patents Number | 8841252 |
| Date of Issue | 23-09-2014 |
| Date of Expiry | 26-12-2017 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pfizer Canada Ulc |
| Brand Description | Pfizer Canada Ulc |
| Prescribed For | Subcutaneous |
| Chemical Name | 5.3 mg / pen |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11465 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Pituitary |
| Patents Number | 6235004 |
| Date of Issue | 22-05-2001 |
| Date of Expiry | 28-01-2019 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pfizer Canada Ulc |
| Brand Description | Pfizer Canada Ulc |
| Prescribed For | Subcutaneous |
| Chemical Name | 12 mg / pen |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11466 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Pituitary and Hypothalamic Hormones and Analogues |
| Patents Number | 9486588 |
| Date of Issue | 08-11-2016 |
| Date of Expiry | 02-07-2022 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pfizer Canada Ulc |
| Brand Description | Pfizer Canada Ulc |
| Prescribed For | Subcutaneous |
| Chemical Name | 0.6 mg / syr |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11467 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Pituitary Hormones |
| Patents Number | 9457154 |
| Date of Issue | 04-10-2016 |
| Date of Expiry | 27-03-2028 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pfizer Canada Ulc |
| Brand Description | Pfizer Canada Ulc |
| Prescribed For | Subcutaneous |
| Chemical Name | 0.8 mg / syr |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11468 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Pituitary Hormones, Anterior |
| Patents Number | RE46363 |
| Date of Issue | 11-04-2017 |
| Date of Expiry | 03-02-2027 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pfizer Canada Ulc |
| Brand Description | Pfizer Canada Ulc |
| Prescribed For | Subcutaneous |
| Chemical Name | 1 mg / syr |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11469 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Recombinant Human Growth Hormone |
| Patents Number | 9687611 |
| Date of Issue | 27-06-2017 |
| Date of Expiry | 27-08-2027 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pfizer Canada Ulc |
| Brand Description | Pfizer Canada Ulc |
| Prescribed For | Subcutaneous |
| Chemical Name | 1.2 mg / syr |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11470 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Somatotropin Agonists |
| Patents Number | 9775953 |
| Date of Issue | 03-10-2017 |
| Date of Expiry | 17-01-2027 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pfizer Canada Ulc |
| Brand Description | Pfizer Canada Ulc |
| Prescribed For | Subcutaneous |
| Chemical Name | 1.4 mg / syr |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11471 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Somatropin and Somatropin Agonists |
| Patents Number | 9861757 |
| Date of Issue | 09-01-2018 |
| Date of Expiry | 20-07-2026 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pfizer Canada Ulc |
| Brand Description | Pfizer Canada Ulc |
| Prescribed For | Subcutaneous |
| Chemical Name | 1.6 mg / syr |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11472 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins |
| Patents Number | 9616180 |
| Date of Issue | 11-04-2017 |
| Date of Expiry | 20-07-2026 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pfizer Canada Ulc |
| Brand Description | Pfizer Canada Ulc |
| Prescribed For | Subcutaneous |
| Chemical Name | 1.8 mg / syr |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11473 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | 7762994 |
| Date of Issue | 27-07-2010 |
| Date of Expiry | 23-11-2024 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pfizer Canada Ulc |
| Brand Description | Pfizer Canada Ulc |
| Prescribed For | Subcutaneous |
| Chemical Name | 2 mg / syr |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11474 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | 8579869 |
| Date of Issue | 12-11-2013 |
| Date of Expiry | 30-12-2023 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pfizer Canada Ulc |
| Brand Description | Pfizer Canada Ulc |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg / pen |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11475 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | 10220155 |
| Date of Issue | 05-03-2019 |
| Date of Expiry | 17-01-2027 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pfizer Canada Ulc |
| Brand Description | Pfizer Canada Ulc |
| Prescribed For | Subcutaneous |
| Chemical Name | 0.2 mg / syr |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11476 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | 10357616 |
| Date of Issue | 23-07-2019 |
| Date of Expiry | 20-01-2026 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Genotropin |
| Company | Pfizer Canada Ulc |
| Brand Description | Pfizer Canada Ulc |
| Prescribed For | Subcutaneous |
| Chemical Name | 0.4 mg / syr |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity GENOTROPIN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. The 5 mg and 12 mg presentations of GENOTROPIN lyophilized powder contain m-cresol as a preservative. Systemic hypersensitivity reactions have been reported with post-marketing use of somatropin products [see WARNINGS AND PRECAUTIONS] . Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, short stature at birth with no catch-up growth, and other causes |
| Route of Administration | Genotropin is a form of human growth hormone important for the growth of bones and muscles. Genotropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short... |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11477 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | 10376652 |
| Date of Issue | 13-08-2019 |
| Date of Expiry | 20-01-2026 |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Humatrope |
| Company | Eli Lilly and Company |
| Brand Description | Eli Lilly and Company |
| Prescribed For | Intramuscular; Subcutaneous |
| Chemical Name | 5 mg/5mL |
| Formulation | HUMATROPE is contraindicated in patients with: Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see WARNINGS AND PRECAUTIONS]. Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death [see WARNINGS AND PRECAUTIONS]. Active malignancy [see WARNINGS AND PRECAUTIONS]. Known hypersensitivity to somatropin or any of the excipients in HUMATROPE. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Active proliferative or severe non-proliferative diabetic retinopathy. Pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, tiredness, muscle pain, weakness, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms (stuffy nose, sneezing, or sore throat) |
| Route of Administration | Humatrope is a form of human growth hormone important for the growth of bones and muscles. Humatrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Humatrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Humatrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Humatrope is a sterile, white, lyophilized powder intended for subcutaneous or intramuscular administration after reconstitution to its liquid form. Humatrope is a highly purified preparation. Phosphoric acid and/or sodium hydroxide may have been added to adjust the pH. Reconstituted solutions have a pH of approximately 7.5. This product is oxygen sensitive. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11478 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Humatrope |
| Company | Eli Lilly and Company |
| Brand Description | Eli Lilly and Company |
| Prescribed For | Intramuscular; Subcutaneous |
| Chemical Name | 6 mg/2.88mL |
| Formulation | HUMATROPE is contraindicated in patients with: Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see WARNINGS AND PRECAUTIONS]. Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death [see WARNINGS AND PRECAUTIONS]. Active malignancy [see WARNINGS AND PRECAUTIONS]. Known hypersensitivity to somatropin or any of the excipients in HUMATROPE. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Active proliferative or severe non-proliferative diabetic retinopathy. Pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, tiredness, muscle pain, weakness, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms (stuffy nose, sneezing, or sore throat) |
| Route of Administration | Humatrope is a form of human growth hormone important for the growth of bones and muscles. Humatrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Humatrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Humatrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Humatrope is a sterile, white, lyophilized powder intended for subcutaneous or intramuscular administration after reconstitution to its liquid form. Humatrope is a highly purified preparation. Phosphoric acid and/or sodium hydroxide may have been added to adjust the pH. Reconstituted solutions have a pH of approximately 7.5. This product is oxygen sensitive. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11479 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Humatrope |
| Company | Eli Lilly and Company |
| Brand Description | Eli Lilly and Company |
| Prescribed For | Intramuscular; Subcutaneous |
| Chemical Name | 12 mg/2.88mL |
| Formulation | HUMATROPE is contraindicated in patients with: Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see WARNINGS AND PRECAUTIONS]. Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death [see WARNINGS AND PRECAUTIONS]. Active malignancy [see WARNINGS AND PRECAUTIONS]. Known hypersensitivity to somatropin or any of the excipients in HUMATROPE. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Active proliferative or severe non-proliferative diabetic retinopathy. Pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, tiredness, muscle pain, weakness, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms (stuffy nose, sneezing, or sore throat) |
| Route of Administration | Humatrope is a form of human growth hormone important for the growth of bones and muscles. Humatrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Humatrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Humatrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Humatrope is a sterile, white, lyophilized powder intended for subcutaneous or intramuscular administration after reconstitution to its liquid form. Humatrope is a highly purified preparation. Phosphoric acid and/or sodium hydroxide may have been added to adjust the pH. Reconstituted solutions have a pH of approximately 7.5. This product is oxygen sensitive. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11480 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Humatrope |
| Company | Eli Lilly and Company |
| Brand Description | Eli Lilly and Company |
| Prescribed For | Intramuscular; Subcutaneous |
| Chemical Name | 24 mg/2.88mL |
| Formulation | HUMATROPE is contraindicated in patients with: Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see WARNINGS AND PRECAUTIONS]. Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death [see WARNINGS AND PRECAUTIONS]. Active malignancy [see WARNINGS AND PRECAUTIONS]. Known hypersensitivity to somatropin or any of the excipients in HUMATROPE. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Active proliferative or severe non-proliferative diabetic retinopathy. Pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, tiredness, muscle pain, weakness, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms (stuffy nose, sneezing, or sore throat) |
| Route of Administration | Humatrope is a form of human growth hormone important for the growth of bones and muscles. Humatrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Humatrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Humatrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Humatrope is a sterile, white, lyophilized powder intended for subcutaneous or intramuscular administration after reconstitution to its liquid form. Humatrope is a highly purified preparation. Phosphoric acid and/or sodium hydroxide may have been added to adjust the pH. Reconstituted solutions have a pH of approximately 7.5. This product is oxygen sensitive. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11481 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Humatrope |
| Company | Eli Lilly & Co. Ltd. |
| Brand Description | Eli Lilly & Co. Ltd. |
| Prescribed For | Intramuscular; Subcutaneous |
| Chemical Name | 5 mg / vial |
| Formulation | HUMATROPE is contraindicated in patients with: Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see WARNINGS AND PRECAUTIONS]. Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death [see WARNINGS AND PRECAUTIONS]. Active malignancy [see WARNINGS AND PRECAUTIONS]. Known hypersensitivity to somatropin or any of the excipients in HUMATROPE. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Active proliferative or severe non-proliferative diabetic retinopathy. Pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, tiredness, muscle pain, weakness, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms (stuffy nose, sneezing, or sore throat) |
| Route of Administration | Humatrope is a form of human growth hormone important for the growth of bones and muscles. Humatrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Humatrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Humatrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Humatrope is a sterile, white, lyophilized powder intended for subcutaneous or intramuscular administration after reconstitution to its liquid form. Humatrope is a highly purified preparation. Phosphoric acid and/or sodium hydroxide may have been added to adjust the pH. Reconstituted solutions have a pH of approximately 7.5. This product is oxygen sensitive. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11482 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Humatrope |
| Company | Eli Lilly & Co. Ltd. |
| Brand Description | Eli Lilly & Co. Ltd. |
| Prescribed For | Intramuscular; Subcutaneous |
| Chemical Name | NA |
| Formulation | HUMATROPE is contraindicated in patients with: Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see WARNINGS AND PRECAUTIONS]. Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death [see WARNINGS AND PRECAUTIONS]. Active malignancy [see WARNINGS AND PRECAUTIONS]. Known hypersensitivity to somatropin or any of the excipients in HUMATROPE. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Active proliferative or severe non-proliferative diabetic retinopathy. Pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, tiredness, muscle pain, weakness, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms (stuffy nose, sneezing, or sore throat) |
| Route of Administration | Humatrope is a form of human growth hormone important for the growth of bones and muscles. Humatrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Humatrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Humatrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Humatrope is a sterile, white, lyophilized powder intended for subcutaneous or intramuscular administration after reconstitution to its liquid form. Humatrope is a highly purified preparation. Phosphoric acid and/or sodium hydroxide may have been added to adjust the pH. Reconstituted solutions have a pH of approximately 7.5. This product is oxygen sensitive. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11483 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Norditropin |
| Company | Novo Nordisk Inc. |
| Brand Description | Novo Nordisk Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg/1.5mL |
| Formulation | NORDITROPIN is contraindicated in patients with:Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see WARNINGS AND PRECAUTIONS].Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death [see WARNINGS AND PRECAUTIONS].Active Malignancy [see WARNINGS AND PRECAUTIONS].Hypersensitivity to NORDITROPIN or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS].Active proliferative or severe non-proliferative diabetic retinopathy.Pediatric patients with closed epiphyses. |
| Physical Appearance | headache, tired feeling, nausea, vomiting, fatigue, muscle pain, joint stiffness or pain, pain in your arms or legs, weakness, cold symptoms (stuffy nose, sneezing, sore throat), or injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising). |
| Route of Administration | Norditropin FlexPro Pen is a form of human growth hormone important for the growth of bones and muscles. Norditropin FlexPro Pen is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | NORDITROPIN is indicated for the treatment of pediatric patients with: |
| Contraindication | NA |
| Side Effects | NORDITROPINis supplied as a sterile solution for subcutaneous use in ready-to-administer prefilled pens with a volume of 1.5 mL or 3 mL. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11484 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Norditropin |
| Company | Novo Nordisk Inc. |
| Brand Description | Novo Nordisk Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg/1.5mL |
| Formulation | NORDITROPIN is contraindicated in patients with:Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see WARNINGS AND PRECAUTIONS].Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death [see WARNINGS AND PRECAUTIONS].Active Malignancy [see WARNINGS AND PRECAUTIONS].Hypersensitivity to NORDITROPIN or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS].Active proliferative or severe non-proliferative diabetic retinopathy.Pediatric patients with closed epiphyses. |
| Physical Appearance | headache, tired feeling, nausea, vomiting, fatigue, muscle pain, joint stiffness or pain, pain in your arms or legs, weakness, cold symptoms (stuffy nose, sneezing, sore throat), or injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising). |
| Route of Administration | Norditropin FlexPro Pen is a form of human growth hormone important for the growth of bones and muscles. Norditropin FlexPro Pen is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | NORDITROPIN is indicated for the treatment of pediatric patients with: |
| Contraindication | NA |
| Side Effects | NORDITROPINis supplied as a sterile solution for subcutaneous use in ready-to-administer prefilled pens with a volume of 1.5 mL or 3 mL. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11485 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Norditropin |
| Company | Novo Nordisk Inc. |
| Brand Description | Novo Nordisk Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 15 mg/1.5mL |
| Formulation | NORDITROPIN is contraindicated in patients with:Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see WARNINGS AND PRECAUTIONS].Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death [see WARNINGS AND PRECAUTIONS].Active Malignancy [see WARNINGS AND PRECAUTIONS].Hypersensitivity to NORDITROPIN or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS].Active proliferative or severe non-proliferative diabetic retinopathy.Pediatric patients with closed epiphyses. |
| Physical Appearance | headache, tired feeling, nausea, vomiting, fatigue, muscle pain, joint stiffness or pain, pain in your arms or legs, weakness, cold symptoms (stuffy nose, sneezing, sore throat), or injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising). |
| Route of Administration | Norditropin FlexPro Pen is a form of human growth hormone important for the growth of bones and muscles. Norditropin FlexPro Pen is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | NORDITROPIN is indicated for the treatment of pediatric patients with: |
| Contraindication | NA |
| Side Effects | NORDITROPINis supplied as a sterile solution for subcutaneous use in ready-to-administer prefilled pens with a volume of 1.5 mL or 3 mL. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11486 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Norditropin |
| Company | Physicians Total Care, Inc. |
| Brand Description | Physicians Total Care, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg/1.5mL |
| Formulation | NORDITROPIN is contraindicated in patients with:Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see WARNINGS AND PRECAUTIONS].Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death [see WARNINGS AND PRECAUTIONS].Active Malignancy [see WARNINGS AND PRECAUTIONS].Hypersensitivity to NORDITROPIN or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS].Active proliferative or severe non-proliferative diabetic retinopathy.Pediatric patients with closed epiphyses. |
| Physical Appearance | headache, tired feeling, nausea, vomiting, fatigue, muscle pain, joint stiffness or pain, pain in your arms or legs, weakness, cold symptoms (stuffy nose, sneezing, sore throat), or injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising). |
| Route of Administration | Norditropin FlexPro Pen is a form of human growth hormone important for the growth of bones and muscles. Norditropin FlexPro Pen is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | NORDITROPIN is indicated for the treatment of pediatric patients with: |
| Contraindication | NA |
| Side Effects | NORDITROPINis supplied as a sterile solution for subcutaneous use in ready-to-administer prefilled pens with a volume of 1.5 mL or 3 mL. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11487 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Norditropin |
| Company | Novo Nordisk |
| Brand Description | Novo Nordisk |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg/1.5mL |
| Formulation | NORDITROPIN is contraindicated in patients with:Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see WARNINGS AND PRECAUTIONS].Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death [see WARNINGS AND PRECAUTIONS].Active Malignancy [see WARNINGS AND PRECAUTIONS].Hypersensitivity to NORDITROPIN or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS].Active proliferative or severe non-proliferative diabetic retinopathy.Pediatric patients with closed epiphyses. |
| Physical Appearance | headache, tired feeling, nausea, vomiting, fatigue, muscle pain, joint stiffness or pain, pain in your arms or legs, weakness, cold symptoms (stuffy nose, sneezing, sore throat), or injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising). |
| Route of Administration | Norditropin FlexPro Pen is a form of human growth hormone important for the growth of bones and muscles. Norditropin FlexPro Pen is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | NORDITROPIN is indicated for the treatment of pediatric patients with: |
| Contraindication | NA |
| Side Effects | NORDITROPINis supplied as a sterile solution for subcutaneous use in ready-to-administer prefilled pens with a volume of 1.5 mL or 3 mL. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11488 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Norditropin |
| Company | Novo Nordisk |
| Brand Description | Novo Nordisk |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg/1.5mL |
| Formulation | NORDITROPIN is contraindicated in patients with:Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see WARNINGS AND PRECAUTIONS].Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death [see WARNINGS AND PRECAUTIONS].Active Malignancy [see WARNINGS AND PRECAUTIONS].Hypersensitivity to NORDITROPIN or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS].Active proliferative or severe non-proliferative diabetic retinopathy.Pediatric patients with closed epiphyses. |
| Physical Appearance | headache, tired feeling, nausea, vomiting, fatigue, muscle pain, joint stiffness or pain, pain in your arms or legs, weakness, cold symptoms (stuffy nose, sneezing, sore throat), or injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising). |
| Route of Administration | Norditropin FlexPro Pen is a form of human growth hormone important for the growth of bones and muscles. Norditropin FlexPro Pen is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | NORDITROPIN is indicated for the treatment of pediatric patients with: |
| Contraindication | NA |
| Side Effects | NORDITROPINis supplied as a sterile solution for subcutaneous use in ready-to-administer prefilled pens with a volume of 1.5 mL or 3 mL. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11489 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Norditropin |
| Company | Novo Nordisk |
| Brand Description | Novo Nordisk |
| Prescribed For | Subcutaneous |
| Chemical Name | 15 mg/1.5mL |
| Formulation | NORDITROPIN is contraindicated in patients with:Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see WARNINGS AND PRECAUTIONS].Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death [see WARNINGS AND PRECAUTIONS].Active Malignancy [see WARNINGS AND PRECAUTIONS].Hypersensitivity to NORDITROPIN or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS].Active proliferative or severe non-proliferative diabetic retinopathy.Pediatric patients with closed epiphyses. |
| Physical Appearance | headache, tired feeling, nausea, vomiting, fatigue, muscle pain, joint stiffness or pain, pain in your arms or legs, weakness, cold symptoms (stuffy nose, sneezing, sore throat), or injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising). |
| Route of Administration | Norditropin FlexPro Pen is a form of human growth hormone important for the growth of bones and muscles. Norditropin FlexPro Pen is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | NORDITROPIN is indicated for the treatment of pediatric patients with: |
| Contraindication | NA |
| Side Effects | NORDITROPINis supplied as a sterile solution for subcutaneous use in ready-to-administer prefilled pens with a volume of 1.5 mL or 3 mL. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11490 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Norditropin |
| Company | Novo Nordisk |
| Brand Description | Novo Nordisk |
| Prescribed For | Subcutaneous |
| Chemical Name | 30 mg/3mL |
| Formulation | NORDITROPIN is contraindicated in patients with:Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see WARNINGS AND PRECAUTIONS].Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death [see WARNINGS AND PRECAUTIONS].Active Malignancy [see WARNINGS AND PRECAUTIONS].Hypersensitivity to NORDITROPIN or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS].Active proliferative or severe non-proliferative diabetic retinopathy.Pediatric patients with closed epiphyses. |
| Physical Appearance | headache, tired feeling, nausea, vomiting, fatigue, muscle pain, joint stiffness or pain, pain in your arms or legs, weakness, cold symptoms (stuffy nose, sneezing, sore throat), or injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising). |
| Route of Administration | Norditropin FlexPro Pen is a form of human growth hormone important for the growth of bones and muscles. Norditropin FlexPro Pen is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | NORDITROPIN is indicated for the treatment of pediatric patients with: |
| Contraindication | NA |
| Side Effects | NORDITROPINis supplied as a sterile solution for subcutaneous use in ready-to-administer prefilled pens with a volume of 1.5 mL or 3 mL. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11491 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Norditropin Nordiflex |
| Company | Novo Nordisk |
| Brand Description | Novo Nordisk |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg / 1.5 mL |
| Formulation | NORDITROPIN is contraindicated in patients with: Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin. Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death. Active Malignancy. Hypersensitivity to NORDITROPIN or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products. Active proliferative or severe non-proliferative diabetic retinopathy. Pediatric patients with closed epiphyses. |
| Physical Appearance | Anxiety blurred vision changes in vision cold sweats coma cool, pale skin decrease in the amount of urine depression excessive sweating extreme weakness flushed, dry skin frequent urination fruit-like breath odor increase in hands and feet size increased hunger increased thirst increased urination increased volume of pale, diluted urine nightmares noisy, rattling breathing pain in the arms or legs seizures shakiness slurred speech stop in menstruation swelling of the fingers or hands troubled breathing at rest |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11492 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Norditropin Nordiflex |
| Company | Novo Nordisk |
| Brand Description | Novo Nordisk |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg / 1.5 mL |
| Formulation | NORDITROPIN is contraindicated in patients with: Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin. Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death. Active Malignancy. Hypersensitivity to NORDITROPIN or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products. Active proliferative or severe non-proliferative diabetic retinopathy. Pediatric patients with closed epiphyses. |
| Physical Appearance | Anxiety blurred vision changes in vision cold sweats coma cool, pale skin decrease in the amount of urine depression excessive sweating extreme weakness flushed, dry skin frequent urination fruit-like breath odor increase in hands and feet size increased hunger increased thirst increased urination increased volume of pale, diluted urine nightmares noisy, rattling breathing pain in the arms or legs seizures shakiness slurred speech stop in menstruation swelling of the fingers or hands troubled breathing at rest |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11493 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Norditropin Nordiflex |
| Company | Novo Nordisk |
| Brand Description | Novo Nordisk |
| Prescribed For | Subcutaneous |
| Chemical Name | 15 mg / 1.5 mL |
| Formulation | NORDITROPIN is contraindicated in patients with: Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin. Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death. Active Malignancy. Hypersensitivity to NORDITROPIN or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products. Active proliferative or severe non-proliferative diabetic retinopathy. Pediatric patients with closed epiphyses. |
| Physical Appearance | Anxiety blurred vision changes in vision cold sweats coma cool, pale skin decrease in the amount of urine depression excessive sweating extreme weakness flushed, dry skin frequent urination fruit-like breath odor increase in hands and feet size increased hunger increased thirst increased urination increased volume of pale, diluted urine nightmares noisy, rattling breathing pain in the arms or legs seizures shakiness slurred speech stop in menstruation swelling of the fingers or hands troubled breathing at rest |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11494 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Norditropin Simplexx |
| Company | Novo Nordisk |
| Brand Description | Novo Nordisk |
| Prescribed For | Subcutaneous |
| Chemical Name | 15 mg / 1.5 mL |
| Formulation | NORDITROPIN is contraindicated in patients with: Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin. Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death. Active Malignancy. Hypersensitivity to NORDITROPIN or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products. Active proliferative or severe non-proliferative diabetic retinopathy. Pediatric patients with closed epiphyses. |
| Physical Appearance | children who are not growing because of low or no growth hormone. Norditropinis a prescription medicine that contains human growth hormone, the same growth hormone made by the human body. children who are short (in stature) and who have Noonan syndrome, Turner syndrome, or were born small (small for gestational age-SGA) and have not caught-up in growth by age 2 to 4 years. children who have Idiopathic Short Stature (ISS). children who are not growing who have Prader-Willi syndrome (PWS). adults who do not make enough growth hormone. |
| Route of Administration | Norditropin is a medicine that contains somatropin, which is a copy of naturally occurring human growth hormone. Growth hormone promotes growth during childhood and adolescence, and also affects the way the body handles proteins, fat and carbohydrates. |
| Recommended Dosage | Norditropin is authorised under a mutual recognition procedure based on an initial authorisation granted by Denmark. In May 2010, the company applied for an additional indication in Denmark and in the following Member States: Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden and the United Kingdom1. The new indication was for the use of Norditropin in children with Prader-Willi syndrome, a rare genetic disease that affects children's growth and development. Although somatropin medicines are already approved in EU Member States for use in Prader-Willi syndrome, the Member States were unable to reach agreement on whether to accept this indication for Norditropin. On 20 April 2011, Denmark referred the matter to the CHMP for arbitration. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11495 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Norditropin Simplexx |
| Company | Novo Nordisk |
| Brand Description | Novo Nordisk |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg / 1.5 mL |
| Formulation | NORDITROPIN is contraindicated in patients with: Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin. Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death. Active Malignancy. Hypersensitivity to NORDITROPIN or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products. Active proliferative or severe non-proliferative diabetic retinopathy. Pediatric patients with closed epiphyses. |
| Physical Appearance | children who are not growing because of low or no growth hormone. Norditropinis a prescription medicine that contains human growth hormone, the same growth hormone made by the human body. children who are short (in stature) and who have Noonan syndrome, Turner syndrome, or were born small (small for gestational age-SGA) and have not caught-up in growth by age 2 to 4 years. children who have Idiopathic Short Stature (ISS). children who are not growing who have Prader-Willi syndrome (PWS). adults who do not make enough growth hormone. |
| Route of Administration | Norditropin is a medicine that contains somatropin, which is a copy of naturally occurring human growth hormone. Growth hormone promotes growth during childhood and adolescence, and also affects the way the body handles proteins, fat and carbohydrates. |
| Recommended Dosage | Norditropin is authorised under a mutual recognition procedure based on an initial authorisation granted by Denmark. In May 2010, the company applied for an additional indication in Denmark and in the following Member States: Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden and the United Kingdom1. The new indication was for the use of Norditropin in children with Prader-Willi syndrome, a rare genetic disease that affects children's growth and development. Although somatropin medicines are already approved in EU Member States for use in Prader-Willi syndrome, the Member States were unable to reach agreement on whether to accept this indication for Norditropin. On 20 April 2011, Denmark referred the matter to the CHMP for arbitration. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11496 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Norditropin Simplexx |
| Company | Novo Nordisk |
| Brand Description | Novo Nordisk |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg / 1.5 mL |
| Formulation | NORDITROPIN is contraindicated in patients with: Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin. Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death. Active Malignancy. Hypersensitivity to NORDITROPIN or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products. Active proliferative or severe non-proliferative diabetic retinopathy. Pediatric patients with closed epiphyses. |
| Physical Appearance | children who are not growing because of low or no growth hormone. Norditropinis a prescription medicine that contains human growth hormone, the same growth hormone made by the human body. children who are short (in stature) and who have Noonan syndrome, Turner syndrome, or were born small (small for gestational age-SGA) and have not caught-up in growth by age 2 to 4 years. children who have Idiopathic Short Stature (ISS). children who are not growing who have Prader-Willi syndrome (PWS). adults who do not make enough growth hormone. |
| Route of Administration | Norditropin is a medicine that contains somatropin, which is a copy of naturally occurring human growth hormone. Growth hormone promotes growth during childhood and adolescence, and also affects the way the body handles proteins, fat and carbohydrates. |
| Recommended Dosage | Norditropin is authorised under a mutual recognition procedure based on an initial authorisation granted by Denmark. In May 2010, the company applied for an additional indication in Denmark and in the following Member States: Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden and the United Kingdom1. The new indication was for the use of Norditropin in children with Prader-Willi syndrome, a rare genetic disease that affects children's growth and development. Although somatropin medicines are already approved in EU Member States for use in Prader-Willi syndrome, the Member States were unable to reach agreement on whether to accept this indication for Norditropin. On 20 April 2011, Denmark referred the matter to the CHMP for arbitration. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11497 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin |
| Company | Genentech, Inc. |
| Brand Description | Genentech, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg/5mg |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-GHD adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day)compared to those receiving placebo |
| Physical Appearance | hives, difficulty breathing, swelling of your face, lips, tongue, or throat, pain in your knees or hips, walking with a limp, ear pain, swelling, warmth, or draining, numbness or tingling in your wrist, hand, or fingers, severe swelling or puffiness in your hands and feet, changes in behavior, vision problems, unusual headaches, changes in the shape or size of a mole, pain or swelling in your joints, severe pain in your upper stomach spreading to your back, nausea, vomiting, increased thirst, increased urination, dry mouth, fruity breath odor, severe headaches, ringing in your ears, dizziness, pain behind your eyes, extreme weakness, weight loss, changes in skin color, severe dizziness, weakness, and tiredness |
| Route of Administration | Nutropin AQ NuSpin 10 is a form of human growth hormone important for the growth of bones and muscles. Nutropin AQ NuSpin 10 is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | Nutropin® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11498 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin |
| Company | Genentech, Inc. |
| Brand Description | Genentech, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg/10mg |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-GHD adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day)compared to those receiving placebo |
| Physical Appearance | hives, difficulty breathing, swelling of your face, lips, tongue, or throat, pain in your knees or hips, walking with a limp, ear pain, swelling, warmth, or draining, numbness or tingling in your wrist, hand, or fingers, severe swelling or puffiness in your hands and feet, changes in behavior, vision problems, unusual headaches, changes in the shape or size of a mole, pain or swelling in your joints, severe pain in your upper stomach spreading to your back, nausea, vomiting, increased thirst, increased urination, dry mouth, fruity breath odor, severe headaches, ringing in your ears, dizziness, pain behind your eyes, extreme weakness, weight loss, changes in skin color, severe dizziness, weakness, and tiredness |
| Route of Administration | Nutropin AQ NuSpin 10 is a form of human growth hormone important for the growth of bones and muscles. Nutropin AQ NuSpin 10 is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | Nutropin® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11499 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin - Kit Pws(10mg) & Liq(10ml) Im Sc |
| Company | Hoffmann La Roche |
| Brand Description | Hoffmann La Roche |
| Prescribed For | Intramuscular; Subcutaneous |
| Chemical Name | NA |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-GHD adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day)compared to those receiving placebo [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome (PWS) in Children Somatropin is contraindicated in patients with PWS who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients. Nutropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed PWS. [see WARNINGS AND PRECAUTIONS]. Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency (GHD) may be an early sign of the presence of a pituitary tumor(or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphysis Somatropin should not be used for growth promotion in pediatric patients with closed epiphysis. Hypersensitivity Nutropin is contraindicated in patients with a known hypersensitivity to somatropin, excipients, or diluent. Localized reactions are the most common hypersensitivity reaction. |
| Physical Appearance | Anxiety blurred vision changes in vision cold sweats coma cool, pale skin decrease in the amount of urine depression excessive sweating extreme weakness flushed, dry skin frequent urination fruit-like breath odor increase in hands and feet size increased hunger increased thirst increased urination increased volume of pale, diluted urine nightmares noisy, rattling breathing pain in the arms or legs seizures shakiness slurred speech stop in menstruation swelling of the fingers or hands troubled breathing at rest |
| Route of Administration | Nutropin AQ NuSpin 10 is a form of human growth hormone important for the growth of bones and muscles. Nutropin AQ NuSpin 10 is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | Nutropin® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11500 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin - Kit Pws(5mg) & Liq(10ml) Im Sc |
| Company | Hoffmann La Roche |
| Brand Description | Hoffmann La Roche |
| Prescribed For | Intramuscular; Subcutaneous |
| Chemical Name | NA |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-GHD adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day)compared to those receiving placebo [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome (PWS) in Children Somatropin is contraindicated in patients with PWS who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients. Nutropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed PWS. [see WARNINGS AND PRECAUTIONS]. Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency (GHD) may be an early sign of the presence of a pituitary tumor(or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphysis Somatropin should not be used for growth promotion in pediatric patients with closed epiphysis. Hypersensitivity Nutropin is contraindicated in patients with a known hypersensitivity to somatropin, excipients, or diluent. Localized reactions are the most common hypersensitivity reaction. |
| Physical Appearance | Anxiety blurred vision changes in vision cold sweats coma cool, pale skin decrease in the amount of urine depression excessive sweating extreme weakness flushed, dry skin frequent urination fruit-like breath odor increase in hands and feet size increased hunger increased thirst increased urination increased volume of pale, diluted urine nightmares noisy, rattling breathing pain in the arms or legs seizures shakiness slurred speech stop in menstruation swelling of the fingers or hands troubled breathing at rest |
| Route of Administration | Nutropin AQ NuSpin 10 is a form of human growth hormone important for the growth of bones and muscles. Nutropin AQ NuSpin 10 is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | Nutropin® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11501 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin AQ |
| Company | Genentech, Inc. |
| Brand Description | Genentech, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg/2mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-GHD adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day)compared to those receiving placebo [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome (PWS) in Children Somatropin is contraindicated in patients with PWS who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients. Nutropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed PWS. [see WARNINGS AND PRECAUTIONS]. Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency (GHD) may be an early sign of the presence of a pituitary tumor(or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphysis Somatropin should not be used for growth promotion in pediatric patients with closed epiphysis. Hypersensitivity Nutropin is contraindicated in patients with a known hypersensitivity to somatropin, excipients, or diluent. Localized reactions are the most common hypersensitivity reaction. |
| Physical Appearance | Anxiety blurred vision changes in vision cold sweats coma cool, pale skin decrease in the amount of urine depression excessive sweating extreme weakness flushed, dry skin frequent urination fruit-like breath odor increase in hands and feet size increased hunger increased thirst increased urination increased volume of pale, diluted urine nightmares noisy, rattling breathing pain in the arms or legs seizures shakiness slurred speech stop in menstruation swelling of the fingers or hands troubled breathing at rest |
| Route of Administration | Nutropin AQ NuSpin 10 is a form of human growth hormone important for the growth of bones and muscles. Nutropin AQ NuSpin 10 is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | Nutropin AQ® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11502 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin AQ - Sc 5mg/ml |
| Company | Hoffmann La Roche |
| Brand Description | Hoffmann La Roche |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg / mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-GHD adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day)compared to those receiving placebo [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome (PWS) in Children Somatropin is contraindicated in patients with PWS who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients. Nutropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed PWS. [see WARNINGS AND PRECAUTIONS]. Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency (GHD) may be an early sign of the presence of a pituitary tumor(or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphysis Somatropin should not be used for growth promotion in pediatric patients with closed epiphysis. Hypersensitivity Nutropin is contraindicated in patients with a known hypersensitivity to somatropin, excipients, or diluent. Localized reactions are the most common hypersensitivity reaction. |
| Physical Appearance | Anxiety blurred vision changes in vision cold sweats coma cool, pale skin decrease in the amount of urine depression excessive sweating extreme weakness flushed, dry skin frequent urination fruit-like breath odor increase in hands and feet size increased hunger increased thirst increased urination increased volume of pale, diluted urine nightmares noisy, rattling breathing pain in the arms or legs seizures shakiness slurred speech stop in menstruation swelling of the fingers or hands troubled breathing at rest |
| Route of Administration | Nutropin AQ NuSpin 10 is a form of human growth hormone important for the growth of bones and muscles. Nutropin AQ NuSpin 10 is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | Nutropin AQ® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11503 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin AQ NuSpin 10 |
| Company | Genentech, Inc. |
| Brand Description | Genentech, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg/2mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-GHD adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day)compared to those receiving placebo [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome (PWS) in Children Somatropin is contraindicated in patients with PWS who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients. Nutropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed PWS. [see WARNINGS AND PRECAUTIONS]. Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency (GHD) may be an early sign of the presence of a pituitary tumor(or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphysis Somatropin should not be used for growth promotion in pediatric patients with closed epiphysis. Hypersensitivity Nutropin is contraindicated in patients with a known hypersensitivity to somatropin, excipients, or diluent. Localized reactions are the most common hypersensitivity reaction. |
| Physical Appearance | Anxiety blurred vision changes in vision cold sweats coma cool, pale skin decrease in the amount of urine depression excessive sweating extreme weakness flushed, dry skin frequent urination fruit-like breath odor increase in hands and feet size increased hunger increased thirst increased urination increased volume of pale, diluted urine nightmares noisy, rattling breathing pain in the arms or legs seizures shakiness slurred speech stop in menstruation swelling of the fingers or hands troubled breathing at rest |
| Route of Administration | Nutropin AQ NuSpin 10 is a form of human growth hormone important for the growth of bones and muscles. Nutropin AQ NuSpin 10 is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | Nutropin AQ® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11504 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin AQ NuSpin 10 |
| Company | Hoffmann La Roche |
| Brand Description | Hoffmann La Roche |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg / 2 mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-GHD adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day)compared to those receiving placebo [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome (PWS) in Children Somatropin is contraindicated in patients with PWS who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients. Nutropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed PWS. [see WARNINGS AND PRECAUTIONS]. Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency (GHD) may be an early sign of the presence of a pituitary tumor(or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphysis Somatropin should not be used for growth promotion in pediatric patients with closed epiphysis. Hypersensitivity Nutropin is contraindicated in patients with a known hypersensitivity to somatropin, excipients, or diluent. Localized reactions are the most common hypersensitivity reaction. |
| Physical Appearance | Anxiety blurred vision changes in vision cold sweats coma cool, pale skin decrease in the amount of urine depression excessive sweating extreme weakness flushed, dry skin frequent urination fruit-like breath odor increase in hands and feet size increased hunger increased thirst increased urination increased volume of pale, diluted urine nightmares noisy, rattling breathing pain in the arms or legs seizures shakiness slurred speech stop in menstruation swelling of the fingers or hands troubled breathing at rest |
| Route of Administration | Nutropin AQ NuSpin 10 is a form of human growth hormone important for the growth of bones and muscles. Nutropin AQ NuSpin 10 is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | Nutropin AQ® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11505 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin AQ NuSpin 20 |
| Company | Genentech, Inc. |
| Brand Description | Genentech, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 20 mg/2mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-GHD adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day)compared to those receiving placebo [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome (PWS) in Children Somatropin is contraindicated in patients with PWS who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients. Nutropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed PWS. [see WARNINGS AND PRECAUTIONS]. Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency (GHD) may be an early sign of the presence of a pituitary tumor(or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphysis Somatropin should not be used for growth promotion in pediatric patients with closed epiphysis. Hypersensitivity Nutropin is contraindicated in patients with a known hypersensitivity to somatropin, excipients, or diluent. Localized reactions are the most common hypersensitivity reaction. |
| Physical Appearance | Anxiety blurred vision changes in vision cold sweats coma cool, pale skin decrease in the amount of urine depression excessive sweating extreme weakness flushed, dry skin frequent urination fruit-like breath odor increase in hands and feet size increased hunger increased thirst increased urination increased volume of pale, diluted urine nightmares noisy, rattling breathing pain in the arms or legs seizures shakiness slurred speech stop in menstruation swelling of the fingers or hands troubled breathing at rest |
| Route of Administration | Nutropin AQ NuSpin 10 is a form of human growth hormone important for the growth of bones and muscles. Nutropin AQ NuSpin 10 is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | Nutropin AQ® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11506 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin AQ NuSpin 20 |
| Company | Hoffmann La Roche |
| Brand Description | Hoffmann La Roche |
| Prescribed For | Subcutaneous |
| Chemical Name | 20 mg / 2 mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-GHD adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day)compared to those receiving placebo [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome (PWS) in Children Somatropin is contraindicated in patients with PWS who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients. Nutropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed PWS. [see WARNINGS AND PRECAUTIONS]. Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency (GHD) may be an early sign of the presence of a pituitary tumor(or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphysis Somatropin should not be used for growth promotion in pediatric patients with closed epiphysis. Hypersensitivity Nutropin is contraindicated in patients with a known hypersensitivity to somatropin, excipients, or diluent. Localized reactions are the most common hypersensitivity reaction. |
| Physical Appearance | Anxiety blurred vision changes in vision cold sweats coma cool, pale skin decrease in the amount of urine depression excessive sweating extreme weakness flushed, dry skin frequent urination fruit-like breath odor increase in hands and feet size increased hunger increased thirst increased urination increased volume of pale, diluted urine nightmares noisy, rattling breathing pain in the arms or legs seizures shakiness slurred speech stop in menstruation swelling of the fingers or hands troubled breathing at rest |
| Route of Administration | Nutropin AQ NuSpin 10 is a form of human growth hormone important for the growth of bones and muscles. Nutropin AQ NuSpin 10 is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | Nutropin AQ® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11507 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin AQ NuSpin 5 |
| Company | Genentech, Inc. |
| Brand Description | Genentech, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg/2mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-GHD adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day)compared to those receiving placebo [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome (PWS) in Children Somatropin is contraindicated in patients with PWS who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients. Nutropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed PWS. [see WARNINGS AND PRECAUTIONS]. Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency (GHD) may be an early sign of the presence of a pituitary tumor(or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphysis Somatropin should not be used for growth promotion in pediatric patients with closed epiphysis. Hypersensitivity Nutropin is contraindicated in patients with a known hypersensitivity to somatropin, excipients, or diluent. Localized reactions are the most common hypersensitivity reaction. |
| Physical Appearance | Anxiety blurred vision changes in vision cold sweats coma cool, pale skin decrease in the amount of urine depression excessive sweating extreme weakness flushed, dry skin frequent urination fruit-like breath odor increase in hands and feet size increased hunger increased thirst increased urination increased volume of pale, diluted urine nightmares noisy, rattling breathing pain in the arms or legs seizures shakiness slurred speech stop in menstruation swelling of the fingers or hands troubled breathing at rest |
| Route of Administration | Nutropin AQ NuSpin 10 is a form of human growth hormone important for the growth of bones and muscles. Nutropin AQ NuSpin 10 is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | Nutropin AQ® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11508 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin AQ NuSpin 5 |
| Company | Hoffmann La Roche |
| Brand Description | Hoffmann La Roche |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg / 2 mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-GHD adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day)compared to those receiving placebo [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome (PWS) in Children Somatropin is contraindicated in patients with PWS who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients. Nutropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed PWS. [see WARNINGS AND PRECAUTIONS]. Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency (GHD) may be an early sign of the presence of a pituitary tumor(or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphysis Somatropin should not be used for growth promotion in pediatric patients with closed epiphysis. Hypersensitivity Nutropin is contraindicated in patients with a known hypersensitivity to somatropin, excipients, or diluent. Localized reactions are the most common hypersensitivity reaction. |
| Physical Appearance | Anxiety blurred vision changes in vision cold sweats coma cool, pale skin decrease in the amount of urine depression excessive sweating extreme weakness flushed, dry skin frequent urination fruit-like breath odor increase in hands and feet size increased hunger increased thirst increased urination increased volume of pale, diluted urine nightmares noisy, rattling breathing pain in the arms or legs seizures shakiness slurred speech stop in menstruation swelling of the fingers or hands troubled breathing at rest |
| Route of Administration | Nutropin AQ NuSpin 10 is a form of human growth hormone important for the growth of bones and muscles. Nutropin AQ NuSpin 10 is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | Nutropin AQ® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11509 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin AQ Pen 10 |
| Company | Genentech, Inc. |
| Brand Description | Genentech, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg/2mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-GHD adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day)compared to those receiving placebo [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome (PWS) in Children Somatropin is contraindicated in patients with PWS who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients. Nutropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed PWS. [see WARNINGS AND PRECAUTIONS]. Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency (GHD) may be an early sign of the presence of a pituitary tumor(or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphysis Somatropin should not be used for growth promotion in pediatric patients with closed epiphysis. Hypersensitivity Nutropin is contraindicated in patients with a known hypersensitivity to somatropin, excipients, or diluent. Localized reactions are the most common hypersensitivity reaction. |
| Physical Appearance | Anxiety blurred vision changes in vision cold sweats coma cool, pale skin decrease in the amount of urine depression excessive sweating extreme weakness flushed, dry skin frequent urination fruit-like breath odor increase in hands and feet size increased hunger increased thirst increased urination increased volume of pale, diluted urine nightmares noisy, rattling breathing pain in the arms or legs seizures shakiness slurred speech stop in menstruation swelling of the fingers or hands troubled breathing at rest |
| Route of Administration | Nutropin AQ NuSpin 10 is a form of human growth hormone important for the growth of bones and muscles. Nutropin AQ NuSpin 10 is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | Nutropin AQ® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11510 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin AQ Pen 20 |
| Company | Genentech, Inc. |
| Brand Description | Genentech, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 20 mg/2mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-GHD adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day)compared to those receiving placebo [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome (PWS) in Children Somatropin is contraindicated in patients with PWS who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients. Nutropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed PWS. [see WARNINGS AND PRECAUTIONS]. Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency (GHD) may be an early sign of the presence of a pituitary tumor(or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphysis Somatropin should not be used for growth promotion in pediatric patients with closed epiphysis. Hypersensitivity Nutropin is contraindicated in patients with a known hypersensitivity to somatropin, excipients, or diluent. Localized reactions are the most common hypersensitivity reaction. |
| Physical Appearance | Anxiety blurred vision changes in vision cold sweats coma cool, pale skin decrease in the amount of urine depression excessive sweating extreme weakness flushed, dry skin frequent urination fruit-like breath odor increase in hands and feet size increased hunger increased thirst increased urination increased volume of pale, diluted urine nightmares noisy, rattling breathing pain in the arms or legs seizures shakiness slurred speech stop in menstruation swelling of the fingers or hands troubled breathing at rest |
| Route of Administration | Nutropin AQ NuSpin 10 is a form of human growth hormone important for the growth of bones and muscles. Nutropin AQ NuSpin 10 is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | Nutropin AQ® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11511 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin AQ Pen Cartridge |
| Company | Hoffmann La Roche |
| Brand Description | Hoffmann La Roche |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg / 2 mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-GHD adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day)compared to those receiving placebo [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome (PWS) in Children Somatropin is contraindicated in patients with PWS who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients. Nutropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed PWS. [see WARNINGS AND PRECAUTIONS]. Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency (GHD) may be an early sign of the presence of a pituitary tumor(or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphysis Somatropin should not be used for growth promotion in pediatric patients with closed epiphysis. Hypersensitivity Nutropin is contraindicated in patients with a known hypersensitivity to somatropin, excipients, or diluent. Localized reactions are the most common hypersensitivity reaction. |
| Physical Appearance | Anxiety blurred vision changes in vision cold sweats coma cool, pale skin decrease in the amount of urine depression excessive sweating extreme weakness flushed, dry skin frequent urination fruit-like breath odor increase in hands and feet size increased hunger increased thirst increased urination increased volume of pale, diluted urine nightmares noisy, rattling breathing pain in the arms or legs seizures shakiness slurred speech stop in menstruation swelling of the fingers or hands troubled breathing at rest |
| Route of Administration | Nutropin AQ NuSpin 10 is a form of human growth hormone important for the growth of bones and muscles. Nutropin AQ NuSpin 10 is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | Nutropin AQ® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11512 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin Depot |
| Company | Genentech, Inc. |
| Brand Description | Genentech, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 13.5 mg/1mL |
| Formulation | Growth hormone should not be initiated to treat patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma, or to patients having acute respiratory failure. Two placebo-controlled clinical trials in non-growth hormone-deficient adult patients (n = 522) with these conditions revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day) compared to those receiving placebo (see WARNINGS). Nutropin Depot (somatropin (rdna origin) for inj) should not be used for growth promotion in pediatric patients with closed epiphyses. Nutropin Depot (somatropin (rdna origin) for inj) should not be used in patients with active neoplasia. GH therapy should be discontinued if evidence of neoplasia develops. Growth hormone is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment (see WARNINGS). Unless patients with Prader-Willi syndrome also have a diagnosis of growth hormone deficiency, Nutropin Depot (somatropin (rdna origin) for inj) is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. |
| Physical Appearance | injection site reactions (nodules, redness, pain, bruising, itching, localized loss of fatty tissue, swelling, or puffiness) headache nausea pain in the legs and feet fever, and vomiting |
| Route of Administration | NA |
| Recommended Dosage | Nutropin Depot® [somatropin (rDNA origin) for injectable suspension] is indicated for the long-term treatment of growth failure due to a lack of adequate endogenous GH secretion. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11513 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin Depot |
| Company | Genentech, Inc. |
| Brand Description | Genentech, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 18 mg/1mL |
| Formulation | Growth hormone should not be initiated to treat patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma, or to patients having acute respiratory failure. Two placebo-controlled clinical trials in non-growth hormone-deficient adult patients (n = 522) with these conditions revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day) compared to those receiving placebo (see WARNINGS). Nutropin Depot (somatropin (rdna origin) for inj) should not be used for growth promotion in pediatric patients with closed epiphyses. Nutropin Depot (somatropin (rdna origin) for inj) should not be used in patients with active neoplasia. GH therapy should be discontinued if evidence of neoplasia develops. Growth hormone is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment (see WARNINGS). Unless patients with Prader-Willi syndrome also have a diagnosis of growth hormone deficiency, Nutropin Depot (somatropin (rdna origin) for inj) is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. |
| Physical Appearance | injection site reactions (nodules, redness, pain, bruising, itching, localized loss of fatty tissue, swelling, or puffiness) headache nausea pain in the legs and feet fever, and vomiting |
| Route of Administration | NA |
| Recommended Dosage | Nutropin Depot® [somatropin (rDNA origin) for injectable suspension] is indicated for the long-term treatment of growth failure due to a lack of adequate endogenous GH secretion. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11514 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropin Depot |
| Company | Genentech, Inc. |
| Brand Description | Genentech, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 22.5 mg/1mL |
| Formulation | Growth hormone should not be initiated to treat patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma, or to patients having acute respiratory failure. Two placebo-controlled clinical trials in non-growth hormone-deficient adult patients (n = 522) with these conditions revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day) compared to those receiving placebo (see WARNINGS). Nutropin Depot (somatropin (rdna origin) for inj) should not be used for growth promotion in pediatric patients with closed epiphyses. Nutropin Depot (somatropin (rdna origin) for inj) should not be used in patients with active neoplasia. GH therapy should be discontinued if evidence of neoplasia develops. Growth hormone is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment (see WARNINGS). Unless patients with Prader-Willi syndrome also have a diagnosis of growth hormone deficiency, Nutropin Depot (somatropin (rdna origin) for inj) is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. |
| Physical Appearance | injection site reactions (nodules, redness, pain, bruising, itching, localized loss of fatty tissue, swelling, or puffiness) headache nausea pain in the legs and feet fever, and vomiting |
| Route of Administration | NA |
| Recommended Dosage | Nutropin Depot® [somatropin (rDNA origin) for injectable suspension] is indicated for the long-term treatment of growth failure due to a lack of adequate endogenous GH secretion. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11515 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Nutropinaq |
| Company | Ipsen Pharma |
| Brand Description | Ipsen Pharma |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg/2ml |
| Formulation | NA |
| Physical Appearance | Sudden death in pediatric patients with Prader-Willi syndrome (PWS) with risk factors includingsevere obesity, history of upper airway obstruction or sleep apnea and unidentified respiratoryinfection, Intracranial tumors, in particular meningiomas, in teenagers/young adults treated with radiationto the head as children for a first neoplasm and somatropin, Glucose intolerance including impaired glucose tolerance/impaired fasting glucose as well asovert diabetes mellitus, Intracranial hypertension, Unmasking of latent central hypothyroidism, Significant diabetic retinopathy , Slipped capital femoral epiphysis in pediatric patients, Progression of preexisting scoliosis in pediatric patients and Fluid retention manifested by edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paraesthesias. |
| Route of Administration | Nutropin AQ NuSpin 10 is a form of human growth hormone important for the growth of bones and muscles. Nutropin AQ NuSpin 10 is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi... |
| Recommended Dosage | Nutropin AQ® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11516 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Omnitrope |
| Company | Sandoz |
| Brand Description | Sandoz |
| Prescribed For | Subcutaneous |
| Chemical Name | 1.5 mg/1.13mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi Syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since GHD may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity Omnitrope is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, feeling tired, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, sore throat. |
| Route of Administration | Omnitrope is a form of human growth hormone important for the growth of bones and muscles. Omnitrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with with Turner syndrome, Prader-Willi syndrome, short stature at birth with no catch-up growth,... |
| Recommended Dosage | Omnitrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Omnitrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Figure 1: Schematic amino acid sequence of human growth hormone including the disulfide bonds |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11517 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Omnitrope |
| Company | Sandoz Inc |
| Brand Description | Sandoz Inc |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg/1.5mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi Syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since GHD may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity Omnitrope is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, feeling tired, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, sore throat. |
| Route of Administration | Omnitrope is a form of human growth hormone important for the growth of bones and muscles. Omnitrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with with Turner syndrome, Prader-Willi syndrome, short stature at birth with no catch-up growth,... |
| Recommended Dosage | Omnitrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Omnitrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Figure 1: Schematic amino acid sequence of human growth hormone including the disulfide bonds |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11518 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Omnitrope |
| Company | Sandoz Inc |
| Brand Description | Sandoz Inc |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg/1.5mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi Syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since GHD may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity Omnitrope is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, feeling tired, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, sore throat. |
| Route of Administration | Omnitrope is a form of human growth hormone important for the growth of bones and muscles. Omnitrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with with Turner syndrome, Prader-Willi syndrome, short stature at birth with no catch-up growth,... |
| Recommended Dosage | Omnitrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Omnitrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Figure 1: Schematic amino acid sequence of human growth hormone including the disulfide bonds |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11519 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Omnitrope |
| Company | Sandoz Inc |
| Brand Description | Sandoz Inc |
| Prescribed For | Subcutaneous |
| Chemical Name | 5.8 mg/1mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi Syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since GHD may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity Omnitrope is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, feeling tired, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, sore throat. |
| Route of Administration | Omnitrope is a form of human growth hormone important for the growth of bones and muscles. Omnitrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with with Turner syndrome, Prader-Willi syndrome, short stature at birth with no catch-up growth,... |
| Recommended Dosage | Omnitrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Omnitrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Figure 1: Schematic amino acid sequence of human growth hormone including the disulfide bonds |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11520 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Omnitrope |
| Company | Sandoz Canada Incorporated |
| Brand Description | Sandoz Canada Incorporated |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg / 1.5 mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi Syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since GHD may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity Omnitrope is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, feeling tired, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, sore throat. |
| Route of Administration | Omnitrope is a form of human growth hormone important for the growth of bones and muscles. Omnitrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with with Turner syndrome, Prader-Willi syndrome, short stature at birth with no catch-up growth,... |
| Recommended Dosage | Omnitrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Omnitrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Figure 1: Schematic amino acid sequence of human growth hormone including the disulfide bonds |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11521 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Omnitrope |
| Company | Sandoz Canada Incorporated |
| Brand Description | Sandoz Canada Incorporated |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg / 1.5 mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi Syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since GHD may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity Omnitrope is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, feeling tired, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, sore throat. |
| Route of Administration | Omnitrope is a form of human growth hormone important for the growth of bones and muscles. Omnitrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with with Turner syndrome, Prader-Willi syndrome, short stature at birth with no catch-up growth,... |
| Recommended Dosage | Omnitrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Omnitrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Figure 1: Schematic amino acid sequence of human growth hormone including the disulfide bonds |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11522 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Omnitrope |
| Company | Sandoz Canada Incorporated |
| Brand Description | Sandoz Canada Incorporated |
| Prescribed For | Subcutaneous |
| Chemical Name | NA |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi Syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since GHD may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity Omnitrope is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, feeling tired, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, sore throat. |
| Route of Administration | Omnitrope is a form of human growth hormone important for the growth of bones and muscles. Omnitrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with with Turner syndrome, Prader-Willi syndrome, short stature at birth with no catch-up growth,... |
| Recommended Dosage | Omnitrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Omnitrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Figure 1: Schematic amino acid sequence of human growth hormone including the disulfide bonds |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11523 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Omnitrope |
| Company | Sandoz Canada Incorporated |
| Brand Description | Sandoz Canada Incorporated |
| Prescribed For | Subcutaneous |
| Chemical Name | 15 mg / 1.5 mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi Syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since GHD may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity Omnitrope is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, feeling tired, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, sore throat. |
| Route of Administration | Omnitrope is a form of human growth hormone important for the growth of bones and muscles. Omnitrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with with Turner syndrome, Prader-Willi syndrome, short stature at birth with no catch-up growth,... |
| Recommended Dosage | Omnitrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Omnitrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Figure 1: Schematic amino acid sequence of human growth hormone including the disulfide bonds |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11524 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Omnitrope |
| Company | Sandoz |
| Brand Description | Sandoz |
| Prescribed For | Subcutaneous |
| Chemical Name | 1.3 mg/ml |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi Syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since GHD may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity Omnitrope is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, feeling tired, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, sore throat. |
| Route of Administration | Omnitrope is a form of human growth hormone important for the growth of bones and muscles. Omnitrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with with Turner syndrome, Prader-Willi syndrome, short stature at birth with no catch-up growth,... |
| Recommended Dosage | Omnitrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Omnitrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Figure 1: Schematic amino acid sequence of human growth hormone including the disulfide bonds |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11525 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Omnitrope |
| Company | Sandoz |
| Brand Description | Sandoz |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg/ml |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi Syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since GHD may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity Omnitrope is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, feeling tired, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, sore throat. |
| Route of Administration | Omnitrope is a form of human growth hormone important for the growth of bones and muscles. Omnitrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with with Turner syndrome, Prader-Willi syndrome, short stature at birth with no catch-up growth,... |
| Recommended Dosage | Omnitrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Omnitrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Figure 1: Schematic amino acid sequence of human growth hormone including the disulfide bonds |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11526 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Omnitrope |
| Company | Sandoz |
| Brand Description | Sandoz |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg/1.5ml |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi Syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since GHD may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity Omnitrope is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, feeling tired, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, sore throat. |
| Route of Administration | Omnitrope is a form of human growth hormone important for the growth of bones and muscles. Omnitrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with with Turner syndrome, Prader-Willi syndrome, short stature at birth with no catch-up growth,... |
| Recommended Dosage | Omnitrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Omnitrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Figure 1: Schematic amino acid sequence of human growth hormone including the disulfide bonds |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11527 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Omnitrope |
| Company | Sandoz |
| Brand Description | Sandoz |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg/1.5ml |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi Syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since GHD may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity Omnitrope is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, feeling tired, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, sore throat. |
| Route of Administration | Omnitrope is a form of human growth hormone important for the growth of bones and muscles. Omnitrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with with Turner syndrome, Prader-Willi syndrome, short stature at birth with no catch-up growth,... |
| Recommended Dosage | Omnitrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Omnitrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Figure 1: Schematic amino acid sequence of human growth hormone including the disulfide bonds |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11528 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Omnitrope |
| Company | Sandoz |
| Brand Description | Sandoz |
| Prescribed For | Subcutaneous |
| Chemical Name | 15 mg/1.5ml |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi Syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see WARNINGS AND PRECAUTIONS]. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since GHD may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity Omnitrope is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, feeling tired, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, sore throat. |
| Route of Administration | Omnitrope is a form of human growth hormone important for the growth of bones and muscles. Omnitrope is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with with Turner syndrome, Prader-Willi syndrome, short stature at birth with no catch-up growth,... |
| Recommended Dosage | Omnitrope is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Omnitrope may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Figure 1: Schematic amino acid sequence of human growth hormone including the disulfide bonds |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11529 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Saizen |
| Company | EMD Serono, Inc. |
| Brand Description | EMD Serono, Inc. |
| Prescribed For | Intramuscular; Subcutaneous |
| Chemical Name | 5 mg/3mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment [see WARNINGS AND PRECAUTIONS]. There have been reports of sudden death when somatropin was used in such patients. SAIZEN is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity SAIZEN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. Benzyl Alcohol SAIZEN reconstituted with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol) should not be administered to patients with a known sensitivity to Benzyl Alcohol |
| Physical Appearance | joint stiffness or pain, muscle pain, pain in your arms or legs, swelling, carpal tunnel syndrome, numbness and burning, headache, tiredness, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), or cold symptoms such as stuffy nose, sneezing, and sore throat. |
| Route of Administration | Saizen is a form of human growth hormone important for the growth of bones and muscles. Saizen is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Saizen is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Saizen may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | SAIZEN is a sterile, non pyrogenic, white, lyophilized powder intended for subcutaneous injection after reconstitution with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol). The reconstituted solution has a pH of 6.5 to 8.5. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11530 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Saizen |
| Company | EMD Serono, Inc. |
| Brand Description | EMD Serono, Inc. |
| Prescribed For | Intramuscular; Subcutaneous |
| Chemical Name | 8.8 mg/3mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment [see WARNINGS AND PRECAUTIONS]. There have been reports of sudden death when somatropin was used in such patients. SAIZEN is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity SAIZEN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. Benzyl Alcohol SAIZEN reconstituted with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol) should not be administered to patients with a known sensitivity to Benzyl Alcohol |
| Physical Appearance | joint stiffness or pain, muscle pain, pain in your arms or legs, swelling, carpal tunnel syndrome, numbness and burning, headache, tiredness, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), or cold symptoms such as stuffy nose, sneezing, and sore throat. |
| Route of Administration | Saizen is a form of human growth hormone important for the growth of bones and muscles. Saizen is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Saizen is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Saizen may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | SAIZEN is a sterile, non pyrogenic, white, lyophilized powder intended for subcutaneous injection after reconstitution with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol). The reconstituted solution has a pH of 6.5 to 8.5. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11531 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Saizen |
| Company | Emd Serono, A Division Of Emd Inc., Canada |
| Brand Description | Emd Serono, A Division Of Emd Inc., Canada |
| Prescribed For | Intramuscular; Subcutaneous |
| Chemical Name | 5 mg / vial |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment [see WARNINGS AND PRECAUTIONS]. There have been reports of sudden death when somatropin was used in such patients. SAIZEN is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity SAIZEN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. Benzyl Alcohol SAIZEN reconstituted with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol) should not be administered to patients with a known sensitivity to Benzyl Alcohol |
| Physical Appearance | joint stiffness or pain, muscle pain, pain in your arms or legs, swelling, carpal tunnel syndrome, numbness and burning, headache, tiredness, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), or cold symptoms such as stuffy nose, sneezing, and sore throat. |
| Route of Administration | Saizen is a form of human growth hormone important for the growth of bones and muscles. Saizen is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Saizen is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Saizen may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | SAIZEN is a sterile, non pyrogenic, white, lyophilized powder intended for subcutaneous injection after reconstitution with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol). The reconstituted solution has a pH of 6.5 to 8.5. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11532 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Saizen |
| Company | Emd Serono, A Division Of Emd Inc., Canada |
| Brand Description | Emd Serono, A Division Of Emd Inc., Canada |
| Prescribed For | Subcutaneous |
| Chemical Name | 5.83 mg / mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment [see WARNINGS AND PRECAUTIONS]. There have been reports of sudden death when somatropin was used in such patients. SAIZEN is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity SAIZEN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. Benzyl Alcohol SAIZEN reconstituted with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol) should not be administered to patients with a known sensitivity to Benzyl Alcohol |
| Physical Appearance | joint stiffness or pain, muscle pain, pain in your arms or legs, swelling, carpal tunnel syndrome, numbness and burning, headache, tiredness, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), or cold symptoms such as stuffy nose, sneezing, and sore throat. |
| Route of Administration | Saizen is a form of human growth hormone important for the growth of bones and muscles. Saizen is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Saizen is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Saizen may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | SAIZEN is a sterile, non pyrogenic, white, lyophilized powder intended for subcutaneous injection after reconstitution with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol). The reconstituted solution has a pH of 6.5 to 8.5. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11533 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Saizen |
| Company | Emd Serono, A Division Of Emd Inc., Canada |
| Brand Description | Emd Serono, A Division Of Emd Inc., Canada |
| Prescribed For | Subcutaneous |
| Chemical Name | 8 mg / mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment [see WARNINGS AND PRECAUTIONS]. There have been reports of sudden death when somatropin was used in such patients. SAIZEN is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity SAIZEN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. Benzyl Alcohol SAIZEN reconstituted with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol) should not be administered to patients with a known sensitivity to Benzyl Alcohol |
| Physical Appearance | joint stiffness or pain, muscle pain, pain in your arms or legs, swelling, carpal tunnel syndrome, numbness and burning, headache, tiredness, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), or cold symptoms such as stuffy nose, sneezing, and sore throat. |
| Route of Administration | Saizen is a form of human growth hormone important for the growth of bones and muscles. Saizen is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Saizen is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency. Saizen may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | SAIZEN is a sterile, non pyrogenic, white, lyophilized powder intended for subcutaneous injection after reconstitution with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol). The reconstituted solution has a pH of 6.5 to 8.5. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11534 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Saizen 10iu - Kit |
| Company | Emd Serono, A Division Of Emd Inc., Canada |
| Brand Description | Emd Serono, A Division Of Emd Inc., Canada |
| Prescribed For | Intramuscular; Subcutaneous |
| Chemical Name | NA |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment [see WARNINGS AND PRECAUTIONS]. There have been reports of sudden death when somatropin was used in such patients. SAIZEN is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity SAIZEN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. Benzyl Alcohol SAIZEN reconstituted with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol) should not be administered to patients with a known sensitivity to Benzyl Alcohol |
| Physical Appearance | hives, difficulty breathing, swelling of your face, lips, tongue, or throat, shortness of breath, coughing, new or increased snoring, pain in your knees or hips, walking with a limp, ear pain, swelling, warmth or drainage from the ear, numbness or tingling in your wrist, hand, or fingers, severe swelling or puffiness in your hands and feet, changes in behavior, vision problems, unusual headaches, changes in the shape or size of a mole, pain or swelling in your joints, severe pain in your upper stomach spreading to your back, nausea, vomiting, increased thirst, increased urination, dry mouth, fruity breath odor, severe headaches, ringing in your ears, dizziness, vision problems, pain behind your eyes, extreme weakness, weight loss, changes in skin color, and tiredness |
| Route of Administration | SAIZEN is a human growth hormone produced by recombinant DNA technology. SAIZEN has 191 amino acid residues and a molecular weight of 22,125 daltons. Its amino acid sequence and structure are identical to the dominant form of human pituitary growth hormone. SAIZEN is produced by a mammalian cell line (mouse C127) that has been modified by the addition of the human growth hormone gene. |
| Recommended Dosage | used to treat the symptoms of Growth Hormone Deficiency. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11535 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Saizen 8.8mg (5.83mg/ml) |
| Company | Emd Serono, A Division Of Emd Inc., Canada |
| Brand Description | Emd Serono, A Division Of Emd Inc., Canada |
| Prescribed For | Subcutaneous |
| Chemical Name | 8.8 mg / vial |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment [see WARNINGS AND PRECAUTIONS]. There have been reports of sudden death when somatropin was used in such patients. SAIZEN is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity SAIZEN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. Benzyl Alcohol SAIZEN reconstituted with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol) should not be administered to patients with a known sensitivity to Benzyl Alcohol |
| Physical Appearance | hives, difficulty breathing, swelling of your face, lips, tongue, or throat, shortness of breath, coughing, new or increased snoring, pain in your knees or hips, walking with a limp, ear pain, swelling, warmth or drainage from the ear, numbness or tingling in your wrist, hand, or fingers, severe swelling or puffiness in your hands and feet, changes in behavior, vision problems, unusual headaches, changes in the shape or size of a mole, pain or swelling in your joints, severe pain in your upper stomach spreading to your back, nausea, vomiting, increased thirst, increased urination, dry mouth, fruity breath odor, severe headaches, ringing in your ears, dizziness, vision problems, pain behind your eyes, extreme weakness, weight loss, changes in skin color, and tiredness |
| Route of Administration | SAIZEN is a human growth hormone produced by recombinant DNA technology. SAIZEN has 191 amino acid residues and a molecular weight of 22,125 daltons. Its amino acid sequence and structure are identical to the dominant form of human pituitary growth hormone. SAIZEN is produced by a mammalian cell line (mouse C127) that has been modified by the addition of the human growth hormone gene. |
| Recommended Dosage | used to treat the symptoms of Growth Hormone Deficiency. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11536 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Saizen Clickeasy |
| Company | EMD Serono, Inc. |
| Brand Description | EMD Serono, Inc. |
| Prescribed For | Intramuscular; Subcutaneous |
| Chemical Name | 8.8 mg/1.51mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment [see WARNINGS AND PRECAUTIONS]. There have been reports of sudden death when somatropin was used in such patients. SAIZEN is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Hypersensitivity SAIZEN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. Benzyl Alcohol SAIZEN reconstituted with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol) should not be administered to patients with a known sensitivity to Benzyl Alcohol. |
| Physical Appearance | hives, difficulty breathing, swelling of your face, lips, tongue, or throat, shortness of breath, coughing, new or increased snoring, pain in your knees or hips, walking with a limp, ear pain, swelling, warmth or drainage from the ear, numbness or tingling in your wrist, hand, or fingers, severe swelling or puffiness in your hands and feet, changes in behavior, vision problems, unusual headaches, changes in the shape or size of a mole, pain or swelling in your joints, severe pain in your upper stomach spreading to your back, nausea, vomiting, increased thirst, increased urination, dry mouth, fruity breath odor, severe headaches, ringing in your ears, dizziness, vision problems, pain behind your eyes, extreme weakness, weight loss, changes in skin color, and tiredness |
| Route of Administration | SAIZEN is a human growth hormone produced by recombinant DNA technology. SAIZEN has 191 amino acid residues and a molecular weight of 22,125 daltons. Its amino acid sequence and structure are identical to the dominant form of human pituitary growth hormone. SAIZEN is produced by a mammalian cell line (mouse C127) that has been modified by the addition of the human growth hormone gene. |
| Recommended Dosage | used to treat the symptoms of Growth Hormone Deficiency. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11537 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Saizenprep |
| Company | EMD Serono, Inc. |
| Brand Description | EMD Serono, Inc. |
| Prescribed For | Intramuscular; Subcutaneous |
| Chemical Name | 8.8 mg/1.51mL |
| Formulation | Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see WARNINGS AND PRECAUTIONS]. Prader-Willi Syndrome In Children Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment [see WARNINGS AND PRECAUTIONS]. There have been reports of sudden death when somatropin was used in such patients. SAIZEN is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See WARNINGS AND PRECAUTIONS]. Hypersensitivity SAIZEN is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS]. Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. Benzyl Alcohol SAIZEN reconstituted with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol) should not be administered to patients with a known sensitivity to Benzyl Alcohol |
| Physical Appearance | Increased mortality in patients with acute critical illness Fatalities in children with Prader-Willi syndrome Neoplasms Glucose intolerance and diabetes mellitus Intracranial hypertension Severe hypersensitivity Fluid retention Hypoadrenalism Hypothyroidism Slipped capital femoral epiphysis in pediatric patients Progression of preexisting scoliosis in pediatric patients Lipoatrophy Pancreatitis |
| Route of Administration | Saizen is a human growth hormone produced by recombinant DNA technology. Saizen has 191 amino acid residues and a molecular weight of 22,125 daltons. Its amino acid sequence and structure are identical to the dominant form of human pituitary growth hormone. Saizen is produced by a mammalian cell line (mouse C127) that has been modified by the addition of the human growth hormone gene. |
| Recommended Dosage | Pediatric Patients Saizen (somatropin) is indicated for the treatment of pediatric patients with growth failure due to inadequate secretion of endogenous growth hormone. Adult Patients Saizen is indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency who meet either of the following two criteria: Adult Onset Patients who have growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or Childhood Onset Patients who were growth hormone deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes. Patients who were treated with somatropin for growth hormone deficiency in childhood and whose epiphyses are closed should be reevaluated before continuation of somatropin therapy at the reduced dose level recommended for growth hormone deficient adults. Confirmation of the diagnosis of adult growth hormone deficiency in both groups involves an appropriate growth hormone provocative test with two exceptions: (1) patients with multiple other pituitary hormone deficiencies due to organic disease; and (2) patients with congenital/genetic growth hormone deficiency. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11538 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Serostim |
| Company | EMD Serono, Inc. |
| Brand Description | EMD Serono, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 8.8 mg/2mL |
| Formulation | Acute Critical IllnessGrowth hormone therapy should not be initiated in patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or acute respiratory failure [see WARNINGS AND PRECAUTIONS ].Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity [see WARNINGS AND PRECAUTIONS].HypersensitivitySEROSTIM is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS].Diabetic RetinopathySomatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, and sore throat. |
| Route of Administration | Serostim is a form of human growth hormone important for the growth of bones and muscles. Serostim is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Serostim is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency and HIV-associated Wasting or Cachexia. Serostim may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | SEROSTIM is a human growth hormone (hGH) produced by recombinant DNA technology. SEROSTIM has 191 amino acid residues and a molecular weight of 22,125 daltons. Its amino acid sequence and structure are identical to the dominant form of human pituitary growth hormone. SEROSTIM is produced by a mammalian cell line (mouse C127) that has been modified by the addition of the hGH gene. SEROSTIM is secreted directly through the cell membrane into the cell-culture medium for collection and purification. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11539 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Serostim |
| Company | EMD Serono, Inc. |
| Brand Description | EMD Serono, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 4 mg/1mL |
| Formulation | Acute Critical IllnessGrowth hormone therapy should not be initiated in patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or acute respiratory failure [see WARNINGS AND PRECAUTIONS ].Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity [see WARNINGS AND PRECAUTIONS].HypersensitivitySEROSTIM is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS].Diabetic RetinopathySomatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, and sore throat. |
| Route of Administration | Serostim is a form of human growth hormone important for the growth of bones and muscles. Serostim is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Serostim is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency and HIV-associated Wasting or Cachexia. Serostim may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | SEROSTIM is a human growth hormone (hGH) produced by recombinant DNA technology. SEROSTIM has 191 amino acid residues and a molecular weight of 22,125 daltons. Its amino acid sequence and structure are identical to the dominant form of human pituitary growth hormone. SEROSTIM is produced by a mammalian cell line (mouse C127) that has been modified by the addition of the hGH gene. SEROSTIM is secreted directly through the cell membrane into the cell-culture medium for collection and purification. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11540 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Serostim |
| Company | EMD Serono, Inc. |
| Brand Description | EMD Serono, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg/1mL |
| Formulation | Acute Critical IllnessGrowth hormone therapy should not be initiated in patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or acute respiratory failure [see WARNINGS AND PRECAUTIONS ].Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity [see WARNINGS AND PRECAUTIONS].HypersensitivitySEROSTIM is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS].Diabetic RetinopathySomatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, and sore throat. |
| Route of Administration | Serostim is a form of human growth hormone important for the growth of bones and muscles. Serostim is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Serostim is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency and HIV-associated Wasting or Cachexia. Serostim may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | SEROSTIM is a human growth hormone (hGH) produced by recombinant DNA technology. SEROSTIM has 191 amino acid residues and a molecular weight of 22,125 daltons. Its amino acid sequence and structure are identical to the dominant form of human pituitary growth hormone. SEROSTIM is produced by a mammalian cell line (mouse C127) that has been modified by the addition of the hGH gene. SEROSTIM is secreted directly through the cell membrane into the cell-culture medium for collection and purification. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11541 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Serostim |
| Company | EMD Serono, Inc. |
| Brand Description | EMD Serono, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 6 mg/1mL |
| Formulation | Acute Critical IllnessGrowth hormone therapy should not be initiated in patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or acute respiratory failure [see WARNINGS AND PRECAUTIONS ].Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity [see WARNINGS AND PRECAUTIONS].HypersensitivitySEROSTIM is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS].Diabetic RetinopathySomatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, and sore throat. |
| Route of Administration | Serostim is a form of human growth hormone important for the growth of bones and muscles. Serostim is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Serostim is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency and HIV-associated Wasting or Cachexia. Serostim may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | SEROSTIM is a human growth hormone (hGH) produced by recombinant DNA technology. SEROSTIM has 191 amino acid residues and a molecular weight of 22,125 daltons. Its amino acid sequence and structure are identical to the dominant form of human pituitary growth hormone. SEROSTIM is produced by a mammalian cell line (mouse C127) that has been modified by the addition of the hGH gene. SEROSTIM is secreted directly through the cell membrane into the cell-culture medium for collection and purification. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11542 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Serostim |
| Company | Emd Serono, A Division Of Emd Inc., Canada |
| Brand Description | Emd Serono, A Division Of Emd Inc., Canada |
| Prescribed For | Subcutaneous |
| Chemical Name | NA |
| Formulation | Acute Critical IllnessGrowth hormone therapy should not be initiated in patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or acute respiratory failure [see WARNINGS AND PRECAUTIONS ].Active MalignancyIn general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity [see WARNINGS AND PRECAUTIONS].HypersensitivitySEROSTIM is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS].Diabetic RetinopathySomatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. |
| Physical Appearance | headache, nausea, vomiting, fatigue, muscle pain, weakness, injection site reactions (redness, soreness, swelling, rash, itching, pain, or bruising), pain in your arms or legs, joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, and sore throat. |
| Route of Administration | Serostim is a form of human growth hormone important for the growth of bones and muscles. Serostim is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Serostim is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency and HIV-associated Wasting or Cachexia. Serostim may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | SEROSTIM is a human growth hormone (hGH) produced by recombinant DNA technology. SEROSTIM has 191 amino acid residues and a molecular weight of 22,125 daltons. Its amino acid sequence and structure are identical to the dominant form of human pituitary growth hormone. SEROSTIM is produced by a mammalian cell line (mouse C127) that has been modified by the addition of the hGH gene. SEROSTIM is secreted directly through the cell membrane into the cell-culture medium for collection and purification. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11543 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Somatropin Biopartners |
| Company | Bio Partners Gmb H |
| Brand Description | Bio Partners Gmb H |
| Prescribed For | Subcutaneous |
| Chemical Name | 2 mg |
| Formulation | NA |
| Physical Appearance | In children, the most common side effects with Somatropin Biopartners (which may affect more than 1 in 10 people) are injection site swelling and development of antibodies (proteins that are produced in response to Somatropin Biopartners). However, these antibodies do not seem to have an effect on the way the medicine works. In adults, the most common side effects (which may affect more than 1 in 10 people) are swelling, mild hyperglycaemia (high blood sugar levels) and headache. |
| Route of Administration | Somatropin Biopartners is a medicine that contains human growth hormone (also known as somatropin). |
| Recommended Dosage | It is used to treat children aged 2 to 18 years who are failing to grow normally because they do not have enough growth hormone. It is also used in adults with a lack of growth hormone who may have either had growth hormone deficiency as children or developed it later during adulthood. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11544 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Somatropin Biopartners |
| Company | Bio Partners Gmb H |
| Brand Description | Bio Partners Gmb H |
| Prescribed For | Subcutaneous |
| Chemical Name | 4 mg |
| Formulation | NA |
| Physical Appearance | In children, the most common side effects with Somatropin Biopartners (which may affect more than 1 in 10 people) are injection site swelling and development of antibodies (proteins that are produced in response to Somatropin Biopartners). However, these antibodies do not seem to have an effect on the way the medicine works. In adults, the most common side effects (which may affect more than 1 in 10 people) are swelling, mild hyperglycaemia (high blood sugar levels) and headache. |
| Route of Administration | Somatropin Biopartners is a medicine that contains human growth hormone (also known as somatropin). |
| Recommended Dosage | It is used to treat children aged 2 to 18 years who are failing to grow normally because they do not have enough growth hormone. It is also used in adults with a lack of growth hormone who may have either had growth hormone deficiency as children or developed it later during adulthood. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11545 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Somatropin Biopartners |
| Company | Bio Partners Gmb H |
| Brand Description | Bio Partners Gmb H |
| Prescribed For | Subcutaneous |
| Chemical Name | 7 mg |
| Formulation | NA |
| Physical Appearance | In children, the most common side effects with Somatropin Biopartners (which may affect more than 1 in 10 people) are injection site swelling and development of antibodies (proteins that are produced in response to Somatropin Biopartners). However, these antibodies do not seem to have an effect on the way the medicine works. In adults, the most common side effects (which may affect more than 1 in 10 people) are swelling, mild hyperglycaemia (high blood sugar levels) and headache. |
| Route of Administration | Somatropin Biopartners is a medicine that contains human growth hormone (also known as somatropin). |
| Recommended Dosage | It is used to treat children aged 2 to 18 years who are failing to grow normally because they do not have enough growth hormone. It is also used in adults with a lack of growth hormone who may have either had growth hormone deficiency as children or developed it later during adulthood. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11546 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Somatropin Biopartners |
| Company | Bio Partners Gmb H |
| Brand Description | Bio Partners Gmb H |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg |
| Formulation | NA |
| Physical Appearance | In children, the most common side effects with Somatropin Biopartners (which may affect more than 1 in 10 people) are injection site swelling and development of antibodies (proteins that are produced in response to Somatropin Biopartners). However, these antibodies do not seem to have an effect on the way the medicine works. In adults, the most common side effects (which may affect more than 1 in 10 people) are swelling, mild hyperglycaemia (high blood sugar levels) and headache. |
| Route of Administration | Somatropin Biopartners is a medicine that contains human growth hormone (also known as somatropin). |
| Recommended Dosage | It is used to treat children aged 2 to 18 years who are failing to grow normally because they do not have enough growth hormone. It is also used in adults with a lack of growth hormone who may have either had growth hormone deficiency as children or developed it later during adulthood. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11547 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Somatropin Biopartners |
| Company | Bio Partners Gmb H |
| Brand Description | Bio Partners Gmb H |
| Prescribed For | Subcutaneous |
| Chemical Name | 20 mg |
| Formulation | NA |
| Physical Appearance | In children, the most common side effects with Somatropin Biopartners (which may affect more than 1 in 10 people) are injection site swelling and development of antibodies (proteins that are produced in response to Somatropin Biopartners). However, these antibodies do not seem to have an effect on the way the medicine works. In adults, the most common side effects (which may affect more than 1 in 10 people) are swelling, mild hyperglycaemia (high blood sugar levels) and headache. |
| Route of Administration | Somatropin Biopartners is a medicine that contains human growth hormone (also known as somatropin). |
| Recommended Dosage | It is used to treat children aged 2 to 18 years who are failing to grow normally because they do not have enough growth hormone. It is also used in adults with a lack of growth hormone who may have either had growth hormone deficiency as children or developed it later during adulthood. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11548 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Tev-tropin |
| Company | Teva |
| Brand Description | Teva |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg/1 |
| Formulation | Tev-Tropin 5 mg reconstituted with bacteriostatic 0.9% sodium chloride injection, USP (normal saline) (benzyl alcohol preserved) should not be administered to patients with a known sensitivity to benzyl alcohol (see WARNINGS). Tev-Tropin 10 mg reconstituted with bacteriostatic water for injection containing 0.33% metacresol should not be used if the patient is allergic to metacresol. Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-growth hormone deficient adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3 to 8 mg/day) compared to those receiving placebo (see WARNINGS). Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment (see WARNINGS). Tev-Tropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. |
| Physical Appearance | headache nausea vomiting fatigue tiredness muscle pain weakness injection site reactions (redness soreness swelling rash itching pain or bruising) pain in your arms or legs joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, or sore throat |
| Route of Administration | NA |
| Recommended Dosage | Tev-Tropin is indicated for the treatment of children who have growth failure due to an inadequate secretion of normal endogenous growth hormone. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11549 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Tev-tropin |
| Company | Teva |
| Brand Description | Teva |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg/1 |
| Formulation | Tev-Tropin 5 mg reconstituted with bacteriostatic 0.9% sodium chloride injection, USP (normal saline) (benzyl alcohol preserved) should not be administered to patients with a known sensitivity to benzyl alcohol (see WARNINGS). Tev-Tropin 10 mg reconstituted with bacteriostatic water for injection containing 0.33% metacresol should not be used if the patient is allergic to metacresol. Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-growth hormone deficient adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3 to 8 mg/day) compared to those receiving placebo (see WARNINGS). Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment (see WARNINGS). Tev-Tropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. |
| Physical Appearance | headache nausea vomiting fatigue tiredness muscle pain weakness injection site reactions (redness soreness swelling rash itching pain or bruising) pain in your arms or legs joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, or sore throat |
| Route of Administration | NA |
| Recommended Dosage | Tev-Tropin is indicated for the treatment of children who have growth failure due to an inadequate secretion of normal endogenous growth hormone. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11550 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Tev-tropin |
| Company | Gate Pharmaceuticals |
| Brand Description | Gate Pharmaceuticals |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg/10mL |
| Formulation | Tev-Tropin 5 mg reconstituted with bacteriostatic 0.9% sodium chloride injection, USP (normal saline) (benzyl alcohol preserved) should not be administered to patients with a known sensitivity to benzyl alcohol (see WARNINGS). Tev-Tropin 10 mg reconstituted with bacteriostatic water for injection containing 0.33% metacresol should not be used if the patient is allergic to metacresol. Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-growth hormone deficient adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3 to 8 mg/day) compared to those receiving placebo (see WARNINGS). Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment (see WARNINGS). Tev-Tropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. |
| Physical Appearance | headache nausea vomiting fatigue tiredness muscle pain weakness injection site reactions (redness soreness swelling rash itching pain or bruising) pain in your arms or legs joint stiffness or pain, or cold symptoms such as stuffy nose, sneezing, or sore throat |
| Route of Administration | NA |
| Recommended Dosage | Tev-Tropin is indicated for the treatment of children who have growth failure due to an inadequate secretion of normal endogenous growth hormone. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11551 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Valtropin |
| Company | Bio Partners Gmb H |
| Brand Description | Bio Partners Gmb H |
| Prescribed For | Subcutaneous |
| Chemical Name | 15 mg/1.5ml |
| Formulation | Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses. Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor. Somatropin should not be used to treat patients with acute critical illness due to complications following open heart surgery, abdominal surgery, or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-growth hormone deficient adult patients (n=522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% versus 19.3%) among somatropin treated patients (doses 5.3-8 mg/day) compared to those receiving placebo. Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment (see WARNINGS). Unless patients with Prader-Willi syndrome also have a diagnosis of growth hormone deficiency, Valtropin (somatropin injection) ® is not indicated for the long-term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. |
| Physical Appearance | headache fever cough respiratory tract infection diarrhea vomiting sore throat ear infection swelling of the extremities runny or stuffy nose flu, and injection site pain |
| Route of Administration | NA |
| Recommended Dosage | Valtropin (somatropin injection) ® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone. |
| Contraindication | NA |
| Side Effects | It is used to treat adenosine deaminase deficiency in people who have a weak immune system. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11552 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Zomacton |
| Company | Ferring Pharmaceuticals Inc. |
| Brand Description | Ferring Pharmaceuticals Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 5 mg/1 |
| Formulation | ZOMACTON is contraindicated in patients with:Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see WARNINGS AND PRECAUTIONS].Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death [see WARNINGS AND PRECAUTIONS].Active malignancy [see WARNINGS AND PRECAUTIONS].Known hypersensitivity to somatropin or any of the excipients in ZOMACTON. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS].Active proliferative or severe non-proliferative diabetic retinopathy.Pediatric patients with closed epiphyses. |
| Physical Appearance | headaches, enlargement of breast tissue in boys (gynecomastia), pancreatitis, and injection-site reactions including pain and bruising |
| Route of Administration | Zomacton is a form of human growth hormone important for the growth of bones and muscles. Zomacton is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Zomacton [somatropin (rDNA origin)] for Injection is a form of growth hormone used to treat children who have growth failure due to an inadequate secretion of normal endogenous growth hormone. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11553 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Zomacton |
| Company | Ferring Pharmaceuticals Inc. |
| Brand Description | Ferring Pharmaceuticals Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 10 mg/1 |
| Formulation | ZOMACTON is contraindicated in patients with:Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see WARNINGS AND PRECAUTIONS].Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death [see WARNINGS AND PRECAUTIONS].Active malignancy [see WARNINGS AND PRECAUTIONS].Known hypersensitivity to somatropin or any of the excipients in ZOMACTON. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS].Active proliferative or severe non-proliferative diabetic retinopathy.Pediatric patients with closed epiphyses. |
| Physical Appearance | headaches, enlargement of breast tissue in boys (gynecomastia), pancreatitis, and injection-site reactions including pain and bruising |
| Route of Administration | Zomacton is a form of human growth hormone important for the growth of bones and muscles. Zomacton is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with short stature due to Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature... |
| Recommended Dosage | Zomacton [somatropin (rDNA origin)] for Injection is a form of growth hormone used to treat children who have growth failure due to an inadequate secretion of normal endogenous growth hormone. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 11554 |
| Therapeutic ID | Th1249 |
| Protein Name | Somatotropin |
| Sequence | >Th1249_Somatotropin FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting point | 76 °C at pH 3.5 |
| Half-life | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.[L10971] |
| Description | Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland.[A228183] Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults.[A228183, L31508] Synthesized in a strain of _Escherichia coli_, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone.[A228188] Recombinant HGH has been commercially available since 1985 after its development by Genentech. [Somatrem] was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.[A228183] Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.[A228188] Recombinant growth hormone is available as a subcutaneous injection for children and adults under a wide variety of brand names. |
| Indication/Disease | Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA).[L31513, L31518] It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.[L31523] It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.[L31518] Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.[L31498] Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.[L31493] |
| Pharmacodynamics | Somatotropin induces growth in nearly every tissue and organ in the body.[L31508] It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced.[L10971] In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.[A228403] The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins.[L31508] The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action _in vivo_, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney [A228398] and suppresses glucose uptake in the adipose tissue.[A228388] In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase.[A228398] The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.[L10971] Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol.[L10971] In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.[A228398] |
| Mechanism of Action | In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels.[A228183] Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.[L10971] Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.[L31508] At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.[A228183] |
| Toxicity | The oral LD50 is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD50 is 710 mg/m3 and dermal LD50 is 1100 mg/kg in rats. The intraperitoneal LD50 in mice is 828 mg/kg.[L31528] Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.[L10971] |
| Metabolism | Information is unavailable. |
| Absorption | When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m2, the Cmax ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the Tmax was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.[L10971] |
| NA | |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Growth hormone receptor,Prolactin receptor |
| Brand Name | Zorbtive |
| Company | EMD Serono, Inc. |
| Brand Description | EMD Serono, Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 8.8 mg/1mL |
| Formulation | Zorbtive® is contraindicated in patients with: active malignancy acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or acute respiratory failure [see WARNINGS AND PRECAUTIONS] active proliferative or severe non-proliferative diabetic retinopathy hypersensitivity to somatropin or any of the excipients of Zorbtive® . Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS] |
| Physical Appearance | hives, difficulty breathing, swelling of your face, lips, tongue, or throat, shortness of breath, coughing, new or increased snoring, pain in your knees or hips, walking with a limp, ear pain, swelling, warmth, or drainage, numbness or tingling in your wrist, hand, or fingers, severe swelling or puffiness in your hands and feet, changes in behavior, vision problems, unusual headaches, changes in the shape or size of a mole, pain or swelling in your joints, severe pain in your upper stomach spreading to your back, nausea, vomiting, increased thirst, increased urination, dry mouth, fruity breath odor, severe headaches, ringing in your ears, dizziness, pain behind your eyes, extreme weakness, severe dizziness, weight loss, changes in skin color, weakness, and tiredness |
| Route of Administration | Zorbtive is a form of human growth hormone important for the growth of bones and muscles. It is similar to the growth hormone your body manufactures. Zorbtive is used to treat Short Bowel Syndrome (SBS) in patients who are on a specialized diet. When used with along with special diet, Zorbtive helps... |
| Recommended Dosage | Zorbtive is a prescription medicine used to treat the symptoms of Growth Hormone Deficiency and Short-bowel Syndrome. Zorbtive may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | Zorbtive® (somatropin) for injection is a human growth hormone produced by recombinant DNA technology for subcutaneous use. Zorbtive® has 191 amino acid residues and a molecular weight of 22,125 daltons. Its amino acid sequence and structure are identical to the dominant form of human pituitary growth hormone. Zorbtive® is produced by a mammalian cell line (mouse C127) that has been modified by the addition of the human growth hormone gene. Zorbtive® is secreted directly through the cell membrane into the cell-culture medium for collection and purification. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |