Pharmacodynamic effects and plasma pharmacokinetics of single doses of cetrorelix acetate in healthy premenopausal women

Objective: To investigate the pharmacodynamic effects and plasma pharmacoki netics of single subcutaneous doses of cetrorelix acetate in healthy premen opausal women. Setting: Phase I clinical research unit. Patient(s): Healthy, premenopausal women aged 19 to 35 years. Intervention(s): 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 e ighth individual cycle day. Transvaginal ultrasound was performed, and bloo d samples for LH, FSH, E-2 were collected during both cycles and for pharma cokinetics up to 168 hours after dosing. The serum hormone levels were dete rmined by electrochemicoluminescence immunoassay and plasma cetrorelix conc entrations by radioimmuno assay. Results: Cetrorelix acetate administration led to a rapid, marked, and reve rsible suppression of serum LH, E-2, and to a lesser extent FSH concentrati ons. 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 rug cetroreli x acetate, peptide base, respectively. The area under the concentration-tim e curve (AUC) and peak cetrorelix concentrations in plasma (C-max) increase d proportionally with dose. Conclusions: Cetrorelix acetate showed pronounced and reversible LH and E-2 suppression and a dose-dependent postponement of LH surge and ovulation af ter single subcutaneous administrations to healthy premenopausal women. Dos e proportionality over the range of 1 mg to 5 mg cetrorelix acetate, peptid e base was demonstrated. (Fertil Steril((R)) 2001;75:316-23. (C) 2001 by Am erican Society for Reproductive Medicine.).