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 me...

Full description

Saved in:
Bibliographic Details
Published in:Journal of clinical pharmacology 2009-02, Vol.49 (2), p.147-154
Main Authors: Ghobadi, Cyrus, Mirhosseini, Nahid, Shiran, Mohammad Reza, Moghadamnia, Ali, Lennard, Martin S., Ledger, William L., Rostami-Hodjegan, Amin
Format: Article
Language:English
Subjects:
Administration, Oral
Adult
Anovulation - drug therapy
Anovulation - etiology
Area Under Curve
clomifene
Clomiphene
Clomiphene - pharmacokinetics
Clomiphene - therapeutic use
Enclomiphene
Female
Fertility Agents, Female - pharmacokinetics
Fertility Agents, Female - therapeutic use
Half-Life
Humans
infertility
Models, Biological
obesity
Obesity - complications
pharmacokinetics
Polycystic Ovary Syndrome - drug therapy
Polycystic Ovary Syndrome - physiopathology
Stereoisomerism
Tissue Distribution
Young Adult
zuclomiphene
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 Cmax, tmax, and AUC of Zu was 15 ± 41 ng/mL, 7 ± 87 h, and 1289 ± 34 ng/mL·h (AUC0–456 h), and that of En was 15 ± 18 ng/mL, 3 ± 68 h, and 65 ± 35 ng/ml·h (AUC0–72 h), respectively. These parameters appeared to be different for Zu from those reported previously in healthy participants, except for tmax. 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.
ISSN:0091-2700
1552-4604
DOI:10.1177/0091270008328096