Pharmacokinetics and safety of oral eletriptan during different phases of the menstrual cycle in healthy volunteers

The purpose of this study was to determine the pharmacokinetics and safety of eletriptan in different phases of the menstrual cycle, Female volunteers (n = 16) with a regular menstrual cycle (28 +/- 4 days) received a single oral dose of 80 mg eletriptan during each of the four cycle phases: phase 1 (menses), days 1 to 4; phase 2 (follicular), days 6 to 10; phase 3 (ovulat ory), days 11 to 13; and phase 4 (luteal), days 21 to 24. Eletriptan plasma concentrations were determined from serial plasma samples taken during a 2 4-hour period after dosing. Blood pressure, pulse rate, and ECG measurement s were performed at baseline, 1 and 24 hours after dosing. No significant d ifferences between phases were observed for maximum plasma concentration (C -max, range of means = 188-234 ng/ml), time to maximum concentration (t(max ), range of means = 1.8-2.5 h), or systemic exposure (area under the curve [AUC], range of means = 1194-1514 ng.h/ml). Although there was a statistica lly significant difference in the terminal phase elimination rate constant (k(el)) between phases 1 and 2 (0.175/h vs. 0.158/h, p = 0.044), the corres ponding difference in terminal phase half-life (t(1/2)) (4.0 h vs. 4.4 h) w as not considered to be clinically relevant. No clinically relevant differe nces in blood pressure, pulse rate, or ECG were observed, and the incidence , nature, and severity of adverse events were similar in all phases. The di fferent phases of the menstrual cycle had no clinically significant effect on the pharmacokinetics, safety, or tolerability of oral 80 mg eletriptan i n healthy females. (C) 2001 the American College of Clinical Pharmacology.