Cetrotide Mechanism of Action

Pharmacotherapeutic group: LHRH-Antagonist. ATC code: G03X.
Cetrotide 0.25 mg inhibits the effects of a natural hormone, called luteinising hormone releasing hormone (LHRH). LHRH regulates the secretion of another hormone, called luteinising hormone (LH), which induces ovulation during the menstrual cycle. Cetrotide 0.25 mg inhibits premature ovulation which is undesirable during hormone treatment for ovarian stimulation as only mature egg cells are suitable for fertilisation.
Pharmacology: Pharmacodynamics: Cetrorelix is a luteinising hormone releasing hormone (LHRH) antagonist. LHRH binds to membrane receptors on pituitary cells. Cetrorelix competes with the binding of endogenous LHRH to these receptors. Due to this mode of action, cetrorelix controls the secretion of gonadotropins (LH and FSH).
Cetrorelix dose-dependently inhibits the secretion of LH and FSH from the pituitary gland. The onset of suppression is virtually immediate and is maintained by continuous treatment, without initial stimulatory effect.
In females, cetrorelix delays the LH surge and consequently ovulation. In women undergoing ovarian stimulation the duration of action of cetrorelix is dose dependent. Following a single dose of 3 mg of cetrorelix a duration of action of at least 4 days has been evaluated. On day 4 the suppression was approximately 70%. At a dose of 0.25 mg per injection repeated injections every 24 hours will maintain the effect of cetrorelix.
In animals as well as in humans, the antagonistic hormonal effects of cetrorelix were fully reversible after termination of treatment.
Pharmacokinetics: The absolute bioavailability of cetrorelix after subcutaneous administration is about 85%.
The total plasma clearance and the renal clearance are 1.2 ml x min^-1 x kg^-1 and 0.1 ml x min^-1 x kg^-1, respectively. The volume of distribution (Vd,area) is 1.1 l x kg^-1. The mean terminal half-lives following intravenous and subcutaneous administration are about 12 h and 30 h, respectively, demonstrating the effect of absorption processes at the injection site. The subcutaneous administration of single doses (0.25 mg to 3 mg cetrorelix) and also daily dosing over 14 days show linear kinetics.