Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
Pharmacotherapeutic group: anti-gonadotropin-releasing hormones, ATC code: H01CC02.

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.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

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.