Single-dose pharmacokinetic study of clomiphene citrate isomers in anovular patients with polycystic ovary disease.

The pharmacokinetics of the zuclomiphene (Zu) and enclomiphene (En) isomers of clomiphene citrate following a single oral dose (50 mg) were characterized for the first time in patients receiving the drug (ie, infertile women with polycystic ovary syndrome). Plasma concentrations of Zu and En were measured in 9 patients from the second day of their menstrual cycle (day 1 of dosing) up to 21 days. The mean (+/- coefficient of variation) of C(max), t(max), and AUC of Zu was 15 +/- 41 ng/mL, 7 +/- 87 h, and 1289 +/- 34 ng/mL.h (AUC(0-456 h)), and that of En was 15 +/- 18 ng/mL, 3 +/- 68 h, and 65 +/- 35 ng/ml.h (AUC(0-72h)), respectively. These parameters appeared to be different for Zu from those reported previously in healthy participants, except for t(max). The pharmacokinetic parameters of En in patients with polycystic ovary syndrome were not generally different from the healthy subjects. The effect of obesity on Zu kinetics was stronger than that on En. The conventional model-dependent pharmacokinetics of clomiphene citrate isomers could not be determined due to a very flat terminal half-life and the long-tailed residence time, signifying the lipophilic nature and potentially extensive distribution of the compound.