Pharmacodynamic effects and plasma pharmacokinetics of single doses of cetrorelix acetate in healthy premenopausal women.
OBJECTIVE
To investigate the pharmacodynamic effects and plasma pharmacokinetics of single subcutaneous doses of cetrorelix acetate in healthy premenopausal women.


METHODS
Phase I clinical research unit.


METHODS
Healthy, premenopausal women aged 19 to 35 years.


METHODS
Single subcutaneous morning doses of cetrorelix acetate (1, 3, or 5 mg peptide base) were investigated in a randomized, single-blind, placebo-controlled, parallel-group design. After a control cycle, 36 women received cetrorelix acetate (12 per dose) and 12 received placebo on the eighth individual cycle day. Transvaginal ultrasound was performed, and blood samples for LH, FSH, E2 were collected during both cycles and for pharmacokinetics up to 168 hours after dosing. The serum hormone levels were determined by electrochemicoluminescence immunoassay and plasma cetrorelix concentrations by radioimmuno assay.


RESULTS
Cetrorelix acetate administration led to a rapid, marked, and reversible suppression of serum LH, E2, and to a lesser extent FSH concentrations. The median intra-individual shifts between treatment and control cycle were -1.0, 4.0, 8.0, and 9.5 days for serum LH maximum and -1.0, 4.5, 7.0, and 10.0 days for ovulation following placebo or 1, 3, and 5 mg cetrorelix acetate, peptide base, respectively. The area under the concentration-time curve (AUC) and peak cetrorelix concentrations in plasma (Cmax) increased proportionally with dose.


CONCLUSIONS
Cetrorelix acetate showed pronounced and reversible LH and E2 suppression and a dose-dependent postponement of LH surge and ovulation after single subcutaneous administrations to healthy premenopausal women. Dose proportionality over the range of 1 mg to 5 mg cetrorelix acetate, peptide base was demonstrated.
Erb
K
K
Clinical Research and Development, ASTA Medica AG, Frankfurt am Main, Germany. katharinaerb@t-online.de
Klipping
C
C
Duijkers
I
I
Pechstein
B
B
Schueler
A
A
Hermann
R
R
D000328:Adult; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D007279:Injections, Subcutaneous; D016014:Linear Models; D007986:Luteinizing Hormone / Q000097:blood; D010060:Ovulation / Q000187:drug effects; D010919:Placebos; D017697:Premenopause
D006727:Hormone Antagonists; D010919:Placebos; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C062876:cetrorelix