Human Reproduction, Vol 13, 2392-2398, Copyright © 1998 by Oxford University Press
IJ Duijkers, C Klipping, WN Willemsen, D Krone, E Schneider, G Niebch and R Hermann
The gonadotrophin-releasing hormone antagonist Cetrorelix is in advanced
clinical development for the control of endogenous gonadotrophin secretion
during the course of a fertility programme. The aim of the present study
was to investigate the pharmacokinetics and pharmacodynamics of Cetrorelix
following single and multiple s.c. administration of different doses.
Thirty-six healthy female volunteers received either 0.25, 0.50 or 1.00 mg
Cetrorelix, in a first menstrual cycle as single dose and in a second cycle
as multiple dose (daily between cycle days 3 and 16). Frequent blood
samples were collected for determination of Cetrorelix, follicle
stimulating hormone (FSH), luteinizing hormone (LH), oestradiol and
progesterone concentrations. Follicular growth was measured by transvaginal
ultrasonography. After single administration of each dose, maximum
Cetrorelix concentrations (Cmax) were reached after 1 h, and Cmax and area
under curve (AUC) increased linearly with the dose. The median terminal
half-life ranged from 5 to 10 h in the three different dose groups. FSH,
LH, oestradiol and progesterone concentrations were suppressed, with a
nadir at 6-12 h after Cetrorelix administration. During multiple
administration, Cmax and AUC also showed dose-linearity. The median
terminal half-life of Cetrorelix varied between 20 and 80 h. A
dose-dependent suppression of FSH, LH and oestradiol concentrations was
observed during treatment. After multiple administration, ovulation was
delayed for 5, 10 and 13 days in the 0.25, 0.50 and 1.00 mg dose groups,
respectively. In conclusion, Cetrorelix showed linear pharmacokinetics, and
effectively delayed the LH surge.
ARTICLES
Single and multiple dose pharmacokinetics and pharmacodynamics of the gonadotrophin-releasing hormone antagonist Cetrorelix in healthy female volunteers
Dinox Medical Investigations, Nijmegen, The Netherlands.
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