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| Primary information |
|---|
| ID | 10507 |
| Therapeutic ID | Th1099 |
| Protein Name | Mecasermin |
| Sequence | >Th1099_Mecasermin
GPETLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA
|
| Molecular Weight | 7649 |
| Chemical Formula | C331H518N94O101S7 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | 5.8 hours |
| Description | E. coli derived, recombinant human insulin-like growth factor-1 (rhIGF-1). It has 70 amino acids in a single chain (identical to the endogenous human protein), with three intramolecular disulfide bridges and a molecular weight of 7649 daltons. |
| Indication/Disease | For the long-term treatment of growth failure in pediatric patients with Primary IGFD or with GH gene deletion who have developed neutralizing antibodies to GH. It is not indicated to treat Secondary IGFD resulting from GH deficiency, malnutrition, hypothyroidism or other causes; it is not a substitute for GH therapy. |
| Pharmacodynamics | Mecasermin is a biosynthetic (recombinant DNA origin) form of human insulin growth factor 1 (IGF-1) designed to replace natural IGF-1 in pediatric patients who are deficient, promoting normalized statural growth. Growth hormones (GH) bind to growth hormone receptors (GHR) in the liver and other tissues, which stimulates the synthesis of IGF-1. In target tissues, IGF-1 activates the IGF-1 receptor, resulting in intracellular signals that stimulate growth. Although many actions of the GH are mediated through IGF-1, the precise roles of GH and IGF-1 have not been fully elucidated. Patients with severe primary IGF-1 deficiency (Primary IGFD) fail to produce adequate levels of IGF-1, due to disruption of the GH pathway used to promote IGF-1 release (possible GH pathway disruptions include mutations in the GHR, post-GHR signaling pathway, and IGF-1 gene defects). |
| Mechanism of Action | Mecasermin supplies recombinant-DNA-origin IGF-1, which binds to the Type I IGF-1 receptor. This receptor exerts intra-cellular signaling activity in a number of processes involved in statural growth, including mitogenesis in multiple tissue types, chondrocyte growth and division along cartilage growth plates, and increases in organ growth. |
| Toxicity | Overdosage of Mecasermin leads to hypoglycemia . One case of acute overdose was treated with IV glucose. Long-term overdosage may result in signs and symptoms of acromegaly. The effects of Mecasermin in human pregnancy has not been studied, however effects on fetal development in animal studies were only seen at doses higher than the maximum recommended human dose based on body surface area. Studies on excretion of the drug in human milk, use in patients under 2 years, use in patients over 65 years, or use in patients with renal or hepatic impairment have not been performed. |
| Metabolism | Information on the metabolism of Mecasermin is not readily available, however it is likely to be metabolized by the liver and kidney like other injectable peptide drugs |
| Absorption | While the bioavailability of rhIGF-1 after subcutaneous administration in healthy subjects has been reported to be close to 100%, the absolute bioavailability of mecasermin given subcutaneously to subjects with primary insulin-like growth factor-1 deficiency (Primary IGFD) has not been determined. |
| 0.257 ± 0.073 L/kg [subjects with severe Primary IGFD] |
| Clearance | Clearance of Mecasermin is inversely proportional to IGF binding protein 3 (IGFBP-3) * Clearance is estimated to be 0.04L/hr/kg at 0.5 micrograms/mL of IGFBP-3 * Clearance is estimated to be 0.01L/hr/kg at 3 micrograms/mL of IGFBP-3 (the median level of IGFBP-3 for patients with normal IGF-1 levels) |
| Categories | Amino Acids, Peptides, and Proteins,Anterior Pituitary Lobe Hormones and Analogues,Biological Factors,Blood Glucose Lowering Agents,Blood Proteins,Growth Substances,Hypoglycemia-Associated Agents,Intercellular Signaling Peptides and Proteins,Peptides,Pituitary and Hypothalamic Hormones and Analogues,Proteins,Somatomedins,Somatotropin Agonists,Somatropin and Somatropin Agonists,Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins |
| Patents Number | US5681814 |
| Date of Issue | 28-Oct-1997 |
| Date of Expiry | 18-Sep-2017 |
| Drug Interaction | NA |
| Target | Insulin-like growth factor 1 receptor,Insulin-like growth factor-binding protein 3,Insulin receptor,Cation-independent mannose-6-phosphate receptor |
| Brand Name | Increlex |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | NA |
| Useful Link 2 | NA |
| Remarks | NA |