| Primary information |
|---|
| ThPP ID | Th1151 |
| Therapeutic Peptide/Protein Name | Somatotropin Recombinant |
| Sequence | FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQT view full sequnce in fasta |
| Functional Classification | Ib |
| Molecular Weight | 22129 |
| Chemical Formula | C990H1532N262O300S7 |
| Isoelectric Point | 5.27 |
| Hydrophobicity | -0.411 |
| Melting Point (℃) | 76 at pH 3 |
| Half Life | N.A. |
| Description | Somatropin (rDNA origin - nonrefrigerated) is a growth hormone. It works by increasing the flow of water, electrolytes, and nutrients into the bowels. |
| Indication/Disease | For treatment of dwarfism, acromegaly and prevention of HIV-induced weight loss |
| Pharmacodynamics | Used in the treatment of dwarfism and growth failure, growth hormone (hGH) stimulates skeletal growth in pediatric patients with growth failure due to a lack of adequate secretion of endogenous GH. Skeletal growth is accomplished at the epiphyseal plates at the ends of a growing bone. Growth and metabolism of epiphyseal plate cells are directly stimulated by GH and one of its mediators, IGF-I (insulin-like growth factor). |
| Mechanism of Action | hGH binds to the human growth hormone receptor (GHR). Upon binding, hGH causes dimerization of GHR, activation of the GHR-associated JAK2 tyrosine kinase, and tyrosyl phosphorylation of both JAK2 and GHR. These events recruit and/or activate a variety of signaling molecules, including MAP kinases, insulin receptor substrates, phosphatidylinositol 3' phosphate kinase, diacylglycerol, protein kinase C, intracellular calcium, and Stat transcription factors. These signaling molecules contribute to the GH-induced changes in enzymatic activity, transport function, and gene expression that ultimately culminate in changes in growth and metabolism. |
| Toxicity | N.A. |
| Metabolism | Both the liver and kidney have been shown to be important metabolizing organs for GH. Animal studies suggest that the kidney is the dominant organ of clearance. GH is filtered at the glomerulus and reabsorbed in the proximal tubules. It is then cleaved within renal cells into its constituent amino acids, which return to the systemic circulation. |
| Absorption | The absolute bioavailability of somatropin after subcutaneous administration in healthy adult males has been determined to be 81 ± 20%. The mean terminal t1/2 after subcutaneous administration is significantly longer than that seen after intravenous administration (2.1 ± 0.43 hours vs. 19.5 ± 3.1 minutes) indicating that the subcutaneous absorption of the compound is slow and rate-limiting. |
| Volume of Distribution | N.A. |
| Clearance | 2.3 ± 1.8 mL/min/kg [GHD patients (IV 33 ng/kg/min)] |
| Categories | Hormone Replacement Agents |
| Patents Number | CA1326439 |
| Date of Issue | 25/01/94 |
| Date of Expiry | 25/01/11 |
| Drug Interaction | N.A. |
| Target | Growth hormone receptor |
| Information of corresponding available drug in the market |
|---|
| Brand Name | NutropinAQ |
| Company | Genentech Inc. |
| Brand Discription | Nutropin [somatropin (rDNA origin) for injection] is a human growth hormone (hGH) produced by recombinant DNA technology. Nutropin has 191 amino acid residues and a molecular weight of 22,125 daltons. The amino acid sequence of the product is identical to that of pituitary-derived hGH. Nutropin may contain not more than fifteen percent deamidated GH at expiration. The deamidated form of GH has been extensively characterized and has been shown to be safe and fully active. |
| Prescribed for | Various brands of this medication are used for the treatment of one of the following medical conditions: growth failure, growth hormone deficiency, intestinal disorder (short bowel syndrome) or HIV-related weight loss or wasting. Somatropin is also used to increase height in children with a certain genetic disorder (Noonan syndrome). |
| Chemical Name | Growth hormon (human), r-DNA derived |
| Formulation | Nutropin is a sterile, white lyophilized powder intended for subcutaneous administration after reconstitution with Bacteriostatic Water for Injection, USP (benzyl alcohol preserved). The reconstituted product is nearly isotonic at a concentration of 5 mg/mL GH and has a pH of approximately 7.4. |
| Physcial Appearnce | Sterile, white lyophilized powder intended for subcutaneous administration after reconstitution with Bacteriostatic Water |
| Route of Administration | Subcutaneous administration |
| Recommended Dosage | Not to exceed 0.006 mg/kg/day SC initially for 6 weeks; may increase up to 0.025 mg/kg/day if patient <35 years of age and up to 0.0125 mg/kg/day if patient >35 years |
| Contraindication | Acute Critical Illness, Prader-Willi Syndrome (PWS) in Children, Active MalignancyIn, Diabetic Retinopathy and Hypersensitivity |
| Side Effects | 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. |
| Useful Link | http://www.rxlist.com/nutropin-drug/overdosage-contraindications.htm |
| PubMed ID | 1496949 |
| 3-D Structure | Th1151 (View) or (Download) |