A study aimed to define the role of CYP2D6 and CYP3A4 in the in vitro metabolism of enclomiphene, the more active isomer of clomiphene. Enclomiphene (25 microM) 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 (1 microM) completely inhibited the metabolism of enclomiphene by all the EM livers and by recombinant CYP2D6 (p<0.001, one way ANOVA). Ketoconazole (2 microM) had no significant effect on enclomiphene metabolism in 3 out of the 4 EM livers. The extent of enclomiphene metabolism was correlated with the amount of CYP2D6 present (p<0.001, Pearson correlation test). The findings indicate that CYP2D6 is primarily responsible for the metabolism of enclomiphene.
CYP2D6 is primarily responsible for the metabolism of clomiphene. Ghobadi C, Gregory A, Crewe HK, Rostami-Hodjegan A, Lennard MS. Drug Metab Pharmacokinet. 2008;23(2):101-5.

A study investigated clomiphene metabolism and action in vitro and in vivo by pharmacogenetic, -kinetic and -dynamic investigations. Human liver microsomes were incubated with clomiphene citrate and nine metabolites were identified by mass spectrometry and tested at the oestrogen receptor for their antagonistic capacity. (E)-4-hydroxyclomiphene and (E)-4-hydroxy-N-desethylclomiphene showed strongest inhibition of the oestrogen receptor activity with 50% inhibitory concentrations of 2.5 and 1.4 nm, respectively. CYP2D6 has been identified as the major enzyme involved in their formation using recombinant CYP450 isozymes as confirmed by inhibition experiments with CYP monoclonal antibodies. The CYP2D6 genotype of 30 human liver donors was correlated with the microsomal formation rate of active metabolites and observed a strong gene-dose effect. A healthy female volunteer study confirmed the in vitro data that the CYP2D6 polymorphism substantially determines the formation of the active clomiphene metabolites. Comparison of the C(max) of (E)-4-hydroxyclomiphene and (E)-4-hydroxy-N-desethylclomiphene showed 8 and 12 times lower concentrations in subjects with non-functional CYP2D6 alleles. The results highlight (E)-4-hydroxyclomiphene and (E)-4-hydroxy-N-desethylclomiphene as the active clomiphene metabolites, the formation of which strongly depends on the polymorphic CYP2D6 enzyme. The data provide evidence of a biological rationale for the variability in the response to clomiphene treatment.
Genetic polymorphism of cytochrome P450 2D6 determines oestrogen receptor activity of the major infertility drug clomiphene via its active metabolites. Mürdter TE, Kerb R, Turpeinen M et al. Hum Mol Genet. 2012 Mar 1;21(5):1145-54

In vitro studies have also shown that delavirdine reduces CYP2C9, CYP2D6, and CYP2C19 activity.
Rescriptor® (delavirdine mesylate) tablets US Prescribing Information, Pfizer Inc. updated May 2008