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| Primary information |
|---|
| ID | 11690 |
| Therapeutic ID | Th1252 |
| Protein Name | Follitropin |
| Sequence | >Th1252_Follitropin
APDVQDCPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCCVAKSYNRVTVMGGFKVENHTACHCSTCYYHKS
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| Molecular Weight | 22672.9 |
| Chemical Formula | C975H1513N267O304S26 |
| Isoelectric Point | 7.5 |
| Hydrophobicity | -0.33 |
| Melting point | 55 °C |
| Half-life | Circulation half life of 3-4 hours, elimination half life of 35-40 hours |
| Description | Follitropin 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 | In women having been diagnosed with primary ovarian failure, it is used in combination with human chorionic gonadotropin (hCG) to assist in ovulation and fertility. In men with hypogonadotrophic hypogonadism, it is used to induce spermatogenesis. 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). |
| 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 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. No studies have been done in nursing mothers. |
| Metabolism | NA |
| Absorption | The absorption rate is the main driving force behind the pharmokinetics of Follitropin alpha as the rate of absorption was found to be slower than the elimination rate after administration subcutaneously and intramuscularly. The bioavailability is approximately 66-76%. The time to peak after subcutaneous injection in healthy volunteers was 8-16 hours in females and 11-20 hours in males. |
| * 8 L [female subjects following intravenous administration of a 300 IU dose] |
| Clearance | * 0.01 1*h-1kg-1 [European women with a single intramuscular dose of 300 IU] * 0.01 1*h-1kg-1 [Japanese women with a single intramuscular dose of 300 IU] |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Follicle-stimulating hormone receptor |
| Brand Name | Pergoveris |
| Company | Merck Europe B.V. |
| Brand Description | Merck Europe B.V. |
| Prescribed For | Subcutaneous |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | The most common side effects reported with Pergoveris (seen in more than 1 patient in 10) are headache, ovarian cysts and injection site reactions (e.g. pain, itching, redness, bruising, swelling or irritation at the site of injection). Treatment can cause overstimulation of the ovaries (known as ovarian hyperstimulation syndrome, OHSS), which can lead to serious medical problems. Mild or moderate OHSS is common, while severe OHSS is uncommon. Thromboembolism (clots in the blood vessels) may occur very rarely, usually associated with severe OHSS. |
| Route of Administration | Pergoveris is a fertility medicine used in women to stimulate the development of follicles, the structures inside the ovaries that contain an egg. |
| Recommended Dosage | Pergoveris is available as a solution for injection in a pre-filled pen or as a powder and solvent to be made up into a solution for injection. Pergoveris is injected under the skin once a day until the patient has developed a suitable follicle, as assessed using ultrasound scans and by measuring blood oestrogen levels. This may take up to 5 weeks. The recommended starting dose is 150 International Units (IU) of follitropin alfa and 75 IU of lutropin alfa once a day, but this should be tailored to the patient’s response. Using less than the recommended starting dose may not be sufficient to stimulate development of a follicle. If necessary, the dose of follitropin alfa can be increased by adding it as a separate medicine, with 7 to 14 days between each dose increase. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |