Pharmacotherapeutic group: anti-gonadotropin-releasing hormones. ATC code: H01CC02.
Pharmacology: Pharmacodynamics: Mechanism of action: 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.
Clinical efficacy and safety: In females, cetrorelix delays the LH surge and consequently ovulation. In women undergoing ovarian stimulation, the duration of action of cetrorelix is dose dependent. 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: Absorption: The absolute bioavailability of cetrorelix after subcutaneous administration is about 85%.
Distribution: The volume of distribution (Vd) is 1.1 L x kg-1.
Elimination: 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 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.
Linearity: The subcutaneous administration of single doses (0.25 mg to 3 mg cetrorelix) and also daily dosing over 14 days show linear kinetics.
Toxicology: Preclinical safety data: Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction.
No target organ toxicity could be observed from acute, subacute and chronic toxicity studies in rats and dogs following subcutaneous administration of cetrorelix. No signs of medicinal product-related local irritation or incompatibility were noted in dogs after intravenous, intra-arterial and paravenous injection when cetrorelix was administered in doses clearly above the intended clinical use in man.
Cetrorelix showed no mutagenic or clastogenic potential in gene and chromosome mutation assays.