| 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 | CA2252535 |
| Date of Issue | 23/06/09 |
| Date of Expiry | 24/04/17 |
| Drug Interaction | N.A. |
| Target | Prolactin receptor |
| Information of corresponding available drug in the market |
|---|
| Brand Name | BioTropin |
| Company | Bio-Technology General (Israel) Ltd. |
| Brand Discription | Bio-Tropin is the brand name for somatropin, a human growth hormone produced by recombinant DNA technology. Bio-Tropin has 191 amino acids and a molecular weight of about 22,124 daltons. Its amino acid sequence is identical to that of human growth hormone of pituitary origin. Bio-Tropin is synthesized in a strain of Escherichia coli modified by insertion of the human growth hormone gene. |
| 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 | Bio-Tropin is provided as a sterile, white, lyophilized powder, available 4 mg presentations. It is intended for subcutaneous administration after reconstitution with bacteriostatic sodium chloride injection, USP, (benzyl alcohol preserved).The diluent for the 4 mg presentation contains solution of 0.9% sodium chloride in water for injection and 0.9% benzyl alcohol as a preservative (bacteriostatic normal saline, USP). A 5 ml vial of the diluent is provided with each dispensed vial of Bio-Tropin. |
| Physcial Appearnce | Sterile, white, lyophilized powder |
| Route of Administration | Subcutaneous administration |
| Recommended Dosage | Growth hormone insufficiency:25-35 µg/kg/day or 0.7-1.0 mg/m2/day, Turner syndrome:50 µg/kg/day or 1.4 mg/m2/day, Chronic Renal Disease:50 µg/kg/day or 1.4 mg/m2/day, In children born small for gestational age (SGA):35 microgram/kg/day or 1 mg/m2/day. A dose of 0.035 mg/kg/day is usually recommended until final height is reached. Treatment should be discontinued after the first year of treatment, if the height velocity SDS is below +1. Treatment should be discontinued if height velocity is < 2cm/year and, if confirmation is required, bone age is>14 years (girls) or >16 years (boys), corresponding to closure of the epiphyseal growth plates. |
| Contraindication | Bio-Tropin should not be used in subjects with closed epiphyses.Patients with evidence of progression of an underlying intracranial lesion should not receive Bio-Tropin. Prior to the initiation of the therapy with Bio-Tropin, intracranial tumors must be inactive and antitumor therapy, including a reasonable period of observation, should be completed. Bio-Tropin should be discontinued if there is evidence of recurrent tumor growth. Bio-Tropin reconstituted with bacteriostatic sodium chloride injection, USP (benzyl alcohol preserved) should not be administered to patients with a known sensitivity to benzyl alcohol. Bio-Tropin is not indicated for the treatment of short stature in genetically confirmed Prader-Willi syndrome. |
| Side Effects | Irritability, Mental Disorder, Insomnia, Depression, Asocial Behaviour, Aggression, Nephrotic Syndrome, Blood Cholesterol Increased |
| Useful Link | http://www.old.health.gov.il/units/pharmacy/trufot/alonim/3241.pdf |
| PubMed ID | 1496949 |
| 3-D Structure | Th1151 (View) or (Download) |