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Pharmacotherapeutic Group: Gonadotrophins. ATC Code: G03GA05/G03GA07.
Pharmacology: Pharmacodynamics: Pergoveris is a preparation of follicle stimulating hormone (FSH) and luteinizing hormone (LH) produced by genetically engineered Chinese Hamster ovary (CHO) cells.
In clinical trials, the efficacy of the combination of follitropin α and lutropin α has been demonstrated in women with hypogonadotropic hypogonadism.
In the stimulation of follicular development in anovulatory women deficient in LH and FSH, the primary effect resulting from administration of lutropin α is an increase in oestradiol secretion by the follicles, the growth of which is stimulated by follitropin α.
In 1 clinical study of women with hypogonadotrophic hypogonadism and an endogenous serum LH concentration <1.2 IU/L, the appropriate dose of lutropin α was investigated. A dose of lutropin α 75 IU daily (in combination with follitropin 150 IU) resulted in adequate follicular development and oestrogen production. A dose of lutropin α 25 IU daily (in combination with follitropin α 150 IU) resulted in insufficient follicular development. Therefore, administration of Pergoveris <75 IU daily may provide inadequate LH-activity to ensure satisfactory follicular development.
Pharmacokinetics: Follitropin α and lutropin α have shown the same pharmacokinetic profile as follitropin α and lutropin α separately.
Follitropin α: Following IV administration, follitropin α is distributed to the extracellular fluid space with an initial half-life (t½) of around 2 hrs and eliminated from the body with a terminal t½ of about 1 day. The steady state volume of distribution and total clearance are 10 L/hr and 0.6 L/hr, respectively. One-eighth (1/8) of the follitropin α dose is excreted in the urine. Following SC administration, the absolute bioavailability is about 70%. Following repeated administration, follitropin α accumulates 3-fold achieving a steady-state within 3-4 days. In women whose endogenous gonadotrophin secretion is suppressed, follitropin α has nevertheless been shown to effectively stimulate follicular development and steroidogenesis, despite unmeasurable LH levels.
Lutropin α: Following IV administration, lutropin α is rapidly distributed with an initial t½ of approximately 1 hr and eliminated from the body with a terminal t½ of about 10-12 hrs. The steady state volume of distribution is approximately 10-14 L. Lutropin α shows linear pharmacokinetics, as assessed by AUC which is directly proportional to the dose administered. Total clearance is around 2 L/hr and <5% of the dose is excreted in the urine. The mean residence time is approximately 5 hrs.
Following SC administration, the absolute bioavailability is approximately 60%; the terminal t½ is slightly prolonged. The lutropin α pharmacokinetics following single- and repeated-administration of lutropin α are comparable and the accumulation ratio of lutropin α is minimal. There is no pharmacokinetic interaction with lutropin α when administered simultaneously.
Preclinical Safety Data: Nonclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated-dose toxicity and genotoxicity.
