enclomiphene and Polycystic-Ovary-Syndrome

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.

Topics: Administration, Oral; Adult; Anovulation; Area Under Curve; Clomiphene; Enclomiphene; Female; Fertility Agents, Female; Half-Life; Humans; Models, Biological; Obesity; Polycystic Ovary Syndrome; Stereoisomerism; Tissue Distribution; Young Adult

The ovulation induction property of ICI 182,780 a pure antiestrogen and enclomiphene citrate (ENC) was carried out in Scotophilus heathi, an Indian tropical vespertillionid bat, during December to February i.e., preovulatory period. This bat ovulates two ova naturally and shows ovulatory asynchrony. The study showed that 100 ìg of ENC followed by 10 IU hCG resulted in significantly lower number of ovulation. Whereas, the pure antiestrogen ICI 182,780 at a dose of 100 ìg followed by 10 IU hCG resulted in ovulation induction (4.2 +/- 0.4), which is significantly different in comparison to other groups. This is possibly the first report of ovulation induction using this pure antiestrogen i.e., ICI 182,780 in any bat as well as in any animal model that exhibits temporary anovulation similar to polycystic ovary disease (PCOD). This antiestrogen may be useful to induce ovulation in PCOD patients.

Topics: Animals; Anovulation; Antineoplastic Agents, Hormonal; Chiroptera; Clomiphene; Enclomiphene; Estradiol; Female; Fertility Agents, Female; Fulvestrant; Humans; India; Ovulation; Polycystic Ovary Syndrome