Monitoring plasma concentrations to individualize treatment with clomiphene citrate.
OBJECTIVE
Recent reports have indicated that a number of individual patient characteristics are responsible for the success or failure of clomiphene citrate treatment. However, a priori individualization of doses in different patients has not been investigated. We examined the thesis that wide variability in the metabolism of the active component (zuclomiphene) contributes to variability in response.


METHODS
The dose-response relationship of clomiphene was established from a meta-analysis of data from 13 published reports. Limited data relating plasma drug concentrations to treatment outcome were examined to determine whether insufficient systemic exposure at a fixed dosage might contribute to therapeutic failure.


RESULTS
A fixed-dosage regimen of 50 mg clomiphene per day is likely to cause ovulation in only 46% of patients; subsequent increment in dosage increases the number of responders but at the expense of considerable delay in individualization of treatment. Case reports indicated that dosage based on plasma drug concentration monitoring could improve patient management, and an algorithm is proposed to facilitate treatment.


CONCLUSIONS
Prospective studies of clomiphene citrate should be performed to confirm the hypothesis that the monitoring of plasma zuclomiphene concentrations can significantly accelerate dose individualization and improve the therapeutic outcome with this "orphan" drug.
Rostami-Hodjegan
Amin
A
Department of Molecular Pharmacology and Pharmacogenetics, University of Sheffield, Sheffield, United Kingdom. a.rostami@sheffield.ac.uk
Lennard
Martin S
MS
Tucker
Geoffrey T
GT
Ledger
William L
WL
D002996:Clomiphene / Q000097:blood* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D010062:Ovulation Induction; D010597:Pharmacogenetics
D002996:Clomiphene