Drug-drug interaction between hydroxybupropion and venlafaxine – a pharmacokinetic study on CYP2D6

Recently, a study showed a dose-dependent inhibition of CYP2D6-mediated metabolism of venlafaxine by bupropion without reporting associations with serum concentrations.

We aimed to investigate the inhibitory effects of bupropion on the pharmacokinetics of venlafaxine, considering not the dose, but the serum concentration of bupropion. Moreover, we aimed to define a threshold in the serum concentration of hydroxybupropion to predict the CYP2D6 poor metabolizer status.

Inpatients with available therapeutic drug monitoring results for venlafaxine and hydroxybupropion were included in the analysis. One sided Spearman correlation was used to test for associations between the hydroxybupropion concentration and the active moiety concentration of venlafaxine, and between the hydroxybupropion concentration and the metabolite-to-parent ratio (MPR) of venlafaxine. Receiver operating characteristic analysis was used to define a threshold in the concentration of hydroxybupropion to predict the CYP2D6 PM status.

A total of 91 patients were included in the analysis. Serum concentration of hydroxybupropion were positively associated with active moiety serum concentrations of venlafaxine (p=0.001), and negatively with the MPR (p=0.02). A switch from CYP2D6 non-PM to PM could be expected for a minimum concentration of hydroxybupropion of 328.5 ng/mL.

We found an increase of the serum concentration of the active moiety of venlafaxine and a decrease of the MPR with increasing hydroxybupropion concentrations. However, as the threshold for phenoconversion to CYP2D6 PM was lower than the mean concentration for the minimum effective dosage of bupropion (150 mg), phenoconversion must be expected in any patient taking bupropion together with venlafaxine, or another CYP2D6 substrate.

Publication History

Article published online:
12 March 2024