A phase I study of the pharmacokinetics, pharmacodynamics, and safety of single-and multiple-dose anastrozole in healthy, premenopausal female volunteers

Objective: To evaluate the pharmacokinetic, pharmacodynamic, and safety profiles of the aromatase inhibitor anastrozole in healthy, premenopausal women. Design: Phase I, single-center study. Setting: Infertility clinic, Patient(s): Twenty-six women with regular ovulatory cycles: 20 received either a single dose of 5 mg, 10 mg, 15 mg, or 20 mg anastrozole, or remained untreated; 6 received five daily doses of 10 mg or 15 mg anastrozole. Intervention(s): Anastrozole was administered on cycle day 2 for the single-dose groups and on days 2-6 for the multiple-dose groups. Ultrasound follicular development and endometrial biopsies were performed. Safety was determined from adverse event reports and laboratory parameters. Main Outcome Measure(s): Pharmacokinetics, pharmacodynamics, and safety. Result(s): The pharmacokinetics of anastrozole were linear, predictable, and consistent with previously published data in healthy volunteers. In the single-dose groups, E-2 levels reached their nadir 3-6 hours after administration, decreasing by an average of 39% from baseline. Follicle-stimulating hormone levels rose by 13%, 52%, 49%, and 75% in the 5-mg, 10-mg, 15-mg, and 20-mg groups, respectively, at approximately 24 hours after dosing. Most subjects recruited just one mature follicle, with no apparent effect on endometrial maturation. No safety concerns were noted. Conclusion(s): Anastrozole was well tolerated and suppressed E-2 levels, with a resultant increase in FSH. (C) 2004 by American Society for Reproductive Medicine.