Prediction of Drug-Drug Interactions with Bupropion and Its Metabolites as CYP2D6 Inhibitors Using a Physiologically-Based Pharmacokinetic Model.

ABSTRACT: The potential of inhibitory metabolites of perpetrator drugs to contribute to drug-drug interactions (DDIs) is uncommon and underestimated. However, the occurrence of unexpected DDI suggests the potential contribution of metabolites to the observed DDI. The aim of this study was to develop a physiologically-based pharmacokinetic (PBPK) model for bupropion and its three primary metabolites-hydroxybupropion, threohydrobupropion and erythrohydrobupropion-based on a mixed "bottom-up" and "top-down" approach and to contribute to the understanding of the involvement and impact of inhibitory metabolites for DDIs observed in the clinic. PK profiles from clinical researches of different dosages were used to verify the bupropion model. Reasonable PK profiles of bupropion and its metabolites were cap

SUBMITTER: Xue C 

PROVIDER: S-EPMC5874814 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature