CYP2D6 is Primarily Responsible for the Metabolism of Clomiphene

• Published in: DRUG METABOLISM AND PHARMACOKINETICS 2008-01, Vol.23 (2), p.101-105
• Main Authors: Ghobadi, Cyrus, Gregory, Anne, Kim Crewe, H., Rostami-Hodjegan, Amin, Lennard, Martin S.
• Format: Article
• Language: English
• Subjects: clomiphene; Clomiphene - metabolism; CYP2D6; Cytochrome P-450 CYP2D6 - physiology; Cytochrome P-450 CYP3A - physiology; Enclomiphene; Humans; Ketoconazole - pharmacology; metabolism; Microsomes, Liver - metabolism; Quinidine - pharmacology; zuclomiphene
• ISSN: 1347-4367; 1880-0920
• DOI: 10.2133/dmpk.23.101

Clomiphene is a first line treatment for anovulation, a common cause of infertility. Response to clomiphene is variable and unpredictable. Tamoxifen is structurally related to clomiphene, and also shows considerable variation in response. CYP2D6 and CYP3A4 are major contributors to the metabolism of tamoxifen. The aim of the present work was to define the role of CYP2D6 and CYP3A4 in the in vitro metabolism of enclomiphene, regarded by some as the more active isomer of clomiphene. Enclomiphene (25μM) was incubated with human liver microsomes (from 4 extensive (EM) and 1 poor metaboliser with respect to CYP2D6) and with microsomes from lymphoblastoid cells expressing CYP2D6. Microsomes from all the EM livers and recombinant CYP2D6 metabolised enclomiphene (the disappearance of drug ranged from 40-60%). No metabolism was detected in microsomes from the PM liver. Quinidine (1μM) completely inhibited the metabolism of enclomiphene by all the EM livers and by recombinant CYP2D6 (p