| 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 | US5288703 |
| Date of Issue | 10/07/94 |
| Date of Expiry | 11/07/11 |
| Drug Interaction | Concomitant glucocorticoid therapy may inhibit the growth promoting effect of Protropin (somatrem) . If glucocorticoid replacement is required, the dose should be carefully adjusted. |
| Target | N.A. |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Protropin |
| Company | Genentech Inc. |
| Brand Discription | Protropin(somatrem for injection) is a polypeptide hormone produced byrecombinant DNA technology. Protropin has 192 amino acidresidues and a molecular weight of about 22,000 daltons. The product contains the identical sequence of 191 amino acids constituting pituitary-derived human growth hormone plus an additional amino acid, methionine, on the N-terminus of the molecule. Protropin is synthesized in a special laboratory strain of E. coli bacteria which has been modified by the addition of the gene for human growth hormone production. Protropin is a highly purified preparation. Biological potency is determined by measuring the increase in body weight induced in hypophysectomized rats. |
| Prescribed for | Protropin is indicated only for the long- term treatment of children who have growth failure due to a lack of adequateendogenous growth hormone secretion. Other etiologies of short stature should be excluded. |
| Chemical Name | Growth hormon (human), r-DNA derived |
| Formulation | Each 5 mg Protropin vial contains 5 mg (approximately 15 IU) somatrem, lyophilized with 40 mg mannitol, and 1.7 mg sodium phosphates (0.1 mg sodium phosphate monobasic and 1.6 mg sodium phosphate dibasic). |
| Physcial Appearnce | Protropin (somatrem) is a sterile, white, lyophilized powder intended forintramuscular or subcutaneous administration after reconstitution withBacteriostatic Water for Injection, USP (benzyl alcohol preserved). |
| Route of Administration | Intramuscular or subcutaneous administration |
| Recommended Dosage | A weekly dosage of 0.30 mg/kg (approximately 0.90 IU/kg) of body weight administered by daily intramuscular or subcutaneous injection is recommended. |
| Contraindication | Protropin (somatrem for injection) should not be used in subjects with closed epiphyses, protropin should not be used in patients with active neoplasia. Growth hormone therapy should be discontinued if evidence of neoplasia develops and when reconstituted with Bacteriostatic Water for Injection, USP (benzyl alcohol preserved) should not be used in patients with a known sensitivity to benzyl alcohol. |
| Side Effects | As with all protein pharmaceuticals, a small percentage of patients may develop antibodies to the protein. Growth hormone antibody binding capacities below 2 mg/L have not been associated with growth attenuation. In some cases when binding capacity exceeds 2 mg/L, growth attenuation has been observed. Common side effects include headache, fatigue, or muscle pain. |
| Useful Link | http://www.rxlist.com/protropin-drug/side-effects-interactions.htm |
| PubMed ID | 1496949 |
| 3-D Structure | Th1151 (View) or (Download) |