Corifollitropin alfa API Manufacturers

General Description:

Corifollitropin alfa, identified by CAS number 195962-23-3, is a notable compound with significant therapeutic applications. Corifollitropin alfa, also known as _Elonva_ is used in women undergoing fertility treatment to stimulate the development of more than one mature egg (oocyte) at a time in the ovaries. This drug used together with _a gonadotropin-releasing hormone (GnRH) antagonist_, a type of medicine also used in fertility treatments. Elonva is available only by prescription . In July 2014, Merck announced the receipt of a Complete Response Letter (CRL) from the U.S. FDA for its New Drug Application for this drug. Corifollitropin alfa is marketed as Elonva in more than 75 countries . Corifollitropin alfa is produced by a method known as ‘recombinant DNA technology’. This means that it is made by cells into which a DNA has been introduced that makes them able to produce corifollitropin alfa . Multiple studies and a meta-analysis suggest that corifollitropin alfa is as efficacious as recombinant FSH in terms of live birth rate, ongoing pregnancy rate, as well as clinical pregnancy rate. The increased in the number of eggs retrieved under corifollitropin alfa regimen represents the elevated effectiveness of this drug, however, warns at the same time against the possibility of an increased risk of ovarian hyperstimulation in the high responder study group of women , .

Indications:

This drug is primarily indicated for: Controlled ovarian stimulation in cases of women who are undergoing fertility treatment to stimulate the development of more than one mature egg simultaneously in the ovaries in combination with a gonadotrophin-releasing hormone (GnRH) antagonist (a type of medicine also used in fertility treatments). Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Corifollitropin alfa undergoes metabolic processing primarily in: The metabolic fate of corifollitropin alfa highly resembles that of endogenous glycoprotein hormones, which predominantly is comprised of kidney clearance and the urinary excretion of the intact protein in parallel to kidney catabolism . This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Corifollitropin alfa are crucial for its therapeutic efficacy: After one single subcutaneous injection of this drug, the maximal serum concentration is 4.24 ng/mL (2.49-7.21 ng/mL1) and is reached 44 hours (35-57 h) post-dose administration. Its absolute bioavailability is 58% (48-70%) . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Corifollitropin alfa is an important consideration for its dosing schedule: Corifollitropin alfa has a longer half-life compared with FSH and thus requires less frequent dosing . Corifollitropin alfa has an elimination half-life of 70 hours (59-82 hours) . This determines the duration of action and helps in formulating effective dosing regimens.

Route of Elimination:

The elimination of Corifollitropin alfa from the body primarily occurs through: Radioactivity labeling showed that the drug was mainly (86%) excreted in the urine. 90% of the radioactivity in serum was identified as corifollitropin alfa, but only 7-15% of the radioactivity in urine was identified as corifollitropin alfa and its dissociation products, the alpha- and beta-subunits (including its CTP part) . Elimination of corifollitropin alfa mainly occurs via the kidneys. The elimination rate of this drug may be reduced in patients with renal insufficiency. Hepatic metabolism contributes to a minor extent to the elimination of corifollitropin alfa . Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Corifollitropin alfa is distributed throughout the body with a volume of distribution of: Distribution, metabolism and elimination of corifollitropin alfa are very similar to other gonadotropins, such as FSH, hCG and LH . After absorption into the blood, corifollitropin alfa is distributed mainly to the ovaries and the kidneys. The steady-state volume of distribution is 9.2 L . Exposure to corifollitropin alfa increases in a linear fashion with the dose within a range of 60 micrograms - 240 micrograms . This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Corifollitropin alfa is a critical factor in determining its safe and effective dosage: 0.13 L/h (0.10-0.18 L/h1). It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Corifollitropin alfa exerts its therapeutic effects through: A single dose of corifollitropin alfa could initiate and sustain multi-follicular growth in patients undergoing controlled ovarian stimulation, such as during in vitro fertilization or intracytoplasmic sperm injection . This drug is structurally similar to follicle stimulating hormone (FSH), a hormone naturally present in females. FSH stimulates the production of eggs (ova) in the ovaries. In corifollitropin alfa, a peptide is attached to the FSH to prolong its activity. As a result, one single dose of the medicine can be administered to stimulate egg production for seven days, replacing daily injections that are normally needed with other FSH medicines . In phase III clinical trials, the number of oocytes retrieved following the administration of corifollitropin alfa was slightly higher compared with the number observed with daily recombinant FSH treatment . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Corifollitropin alfa functions by: Corifollitropin alfa is a long-lasting single injection fusion protein which lacks luteinizing hormone (LH) activity. Only one injection is needed for the first 7 days, which replaces the first 7 daily injections of traditional follicle stimulating hormone (FSH). It is a follicle-stimulation hormone (human α-subunit reduced), a combination of follicle stimulation hormone (human β-subunit reduced) fusion protein with 118-145-chorionic gonadotropin (human β-subunit) . Frequent, repetitive injections increase stress and error rates, and are often a burden for women, leading to therapy noncompliance . The agent comprises an alpha-subunit, which is identical to that of FSH, and a beta-subunit, which is produced by the fusion of the C-terminal peptide from the beta-subunit of chorionic gonadotropin to the beta-subunit of FSH . Corifollitropin alfa serves as a sustained follicle stimulant that has similar pharmacological effects to recombinant follicle stimulating hormone (rFSH), however, with a relatively long elimination half-life, resulting in a longer duration of action. This is achieved using site-directed mutagenesis and gene transfer techniques to create a glycoprotein that consists of an α-subunit that is identical to human follicle stimulating hormone (FSH) noncovalently bound to a _β-subunit_ comprised of a complete _β-chain_ of human FSH elongated by the carboxyterminal peptide of the β-subunit of human chorionic gonadotrophin (hCG) . This unit interacts with the FSH receptor to stimulate the release of oocytes. Corifollitropin alfa does not demonstrate any intrinsic LH/hCG activity . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Corifollitropin alfa belongs to the None, classified under the direct parent group Peptides. This compound is a part of the Organic Compounds, falling under the Organic Acids superclass, and categorized within the Carboxylic Acids and Derivatives class, specifically within the Amino Acids, Peptides, and Analogues subclass.

Categories:

Corifollitropin alfa is categorized under the following therapeutic classes: Drugs that are Mainly Renally Excreted, Follicle Stimulating Hormone, Genito Urinary System and Sex Hormones, Gonadotropins, Gonadotropins, Pituitary, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Peptide Hormones, Pituitary Hormones, Pituitary Hormones, Anterior, Recombinant Proteins, Sex Hormones and Modulators of the Genital System. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Corifollitropin alfa include:

• Molecular Weight: 25398.0389