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| Primary information |
|---|
| ID | 10374 |
| Therapeutic ID | Th1055 |
| Protein Name | Follitropin beta |
| Sequence | >Th1055_Follitropin_beta
APDVQDCPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCCVAKSYNRVTVMGGFKVENHTACHCSTCYYHKS
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| Molecular Weight | 22672.9 |
| Chemical Formula | C975H1513N267O304S26 |
| Isoelectric Point | 7.5 |
| Hydrophobicity | -0.33 |
| Melting point | 55 |
| Half-life | Circulation half life of 3-4 hours, elimination half life of 35-40 hours |
| Description | Follitropin beta is a human follicle stimulating hormone (FSH) preparation of recombinant DNA origin, which consists of two non-covalently linked, non-identical glycoproteins designated as the alpha- and beta- subunits. The alpha- and beta- subunits have 92 and 111 amino acids. The alpha subunit is glycosylated at Asn 51 and Asn 78 while the beta subunit is glycosylated at Asn 7 and Asn 24. Follitropin beta is produced in genetically engineered Chinese hamster cell lines (CHO). The nomenclature “beta†differentiates it from another recombinant human FSH product that was marketed earlier as follitropin alpha. Follitropin is important in the development of follicles produced by the ovaries. Given by subcutaneous injection, it is used in combination with human chorionic gonadotropin (hCG) to assist in ovulation and fertility. Follitropin may also be used to cause the ovary to produce several follicles, which can then be harvested for use in gamete intrafallopian transfer (GIFT) or in vitro fertilization (IVF). Numerous physio-chemical tests and bioassays indicate that follitropin beta and follitropin alpha are indistinguishable. However, a more recent study showed there is may be a slight clinical difference, with the alpha form tending towards a higher pregnancy rate and the beta form tending towards a lower pregnancy rate, but with significantly higher estradiol (E2) levels. Structural analysis shows that the amino acid sequence of follitropin beta is identical to that of natural human follicle stimulating hormone (FSH). Further, the ogliosaccharide side chains are very similar, but not completely identical to that of natural FSH. However, these small differences do not affect the bioactivity compared to natural FSH. |
| Indication/Disease | For treatment of female infertility |
| Pharmacodynamics | Used for the treatment of female infertility, Follitropin beta or follicle stimulating hormone (FSH) stimulates ovarian follicular growth in women who do not have primary ovarian failure. FSH, the active component of Follitropin beta is the primary hormone responsible for follicular recruitment and development. |
| Mechanism of Action | Follitropin alpha is a recombinant form of endogenous follicle stimulating hormone (FSH). FSH binds to the follicle stimulating hormone receptor which is a G-coupled transmembrane receptor. Binding of the FSH to its receptor seems to induce phosphorylation and activation of the PI3K (Phosphatidylinositol-3-kinase) and Akt signaling pathway, which is known to regulate many other metabolic and related survival/maturation functions in cells. |
| Toxicity | Headaches, ovarian cysts, nausea and upper respiratory tract infections occurred in more than 10% of women in clinical trials. In men, the most serious adverse events reported were testicular surgery for cryptorchidism which existed prestudy, hemoptysis, an infected pilonidal cyst, and lymphadenopathy associated with an Epstein-Barr viral infection. Other concerns include overstimulation of the ovaries, pulmonary and vascular complications and multiple births. Post-marketing reports revealed hypersensitivity reactions including anaphylactoid reactions and asthma. Follitropin is contraindicated in pregnant women. |
| Metabolism | NA |
| Absorption | bioavailability is approximately 66-76%. |
| 8 L [female subjects following intravenous administration of a 300 IU dose] |
| Clearance | 0.011 /h/kg [European women with a single intramuscular dose of 300 IU] 0.011 /h/kg [Japanese women with a single intramuscular dose of 300 IU] |
| Categories | Amino Acids, Peptides, and Proteins, Follicle Stimulating Hormone, Genito Urinary System and Sex Hormones, Gonadotropins, Gonadotropins and Antigonadotropins, Gonadotropins, Pituitary, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Peptide Hormones, Peptides, Pituitary Hormones, Pituitary Hormones, Anterior, Proteins, Sex Hormones and Modulators of the Genital System, Thyroid Products |
| Patents Number | CA2037884 |
| Date of Issue | 21-Oct-2003 |
| Date of Expiry | 8-Mar-2011 |
| Drug Interaction | NA |
| Target | NA |
| Brand Name | Fertavid |
| Company | Merck Sharp & Dohme B.V. |
| Brand Description | Merck Sharp & Dohme B.V. |
| 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 |