- Cytochrome P450 enzyme substrate: CYP2D6 and CYP2B6
- Action to be taken: Caution with close monitoring
- Rationale: In vitro findings suggest that CYP2B6 is the principal isoenzyme involved in the formation of hydroxybupropion, while cytochrome P450 isoenzymes are not involved in the formation of threohydrobupropion. Because bupropion is extensively metabolized, there is the potential for drug-druginteractions, particularly with those agents that are metabolized by CYP2B6 isoenzyme. Although bupropion is not metabolized by CYP2D6, there is the potential for drug-drug interactions when bupropion is co-administered with drugs metabolized by this isoenzyme. In vitro data showed that cannabis is a potential substrate of CYP2D6 and that it exhibits weak inhibitory activity on CYP2B6 and CYP2D6 enzymes. Based on available data cannabis may increase exposure of bupropion.
- Wellbutrin (bupropion) package insert. GlaxoSmithKline Research Triangle Park, NC, 2006
- Watanabe K, Yamaori S, Funahashi T, et al. Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sci. 2007;80:1415-1419.
- Stout SM, Cimino NM. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev. 2014;46:86-95.