Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: Potential drug interactions with bupropion

Since antiretroviral drugs are known to inhibit many cytochrome P450 isofor ms, the inhibition of CYP2B6 by non-nucleoside reverse transcriptase inhibi tors and viral protease inhibitors was studied in vitro in human liver micr osomes using bupropion hydroxylation as the CYP2B6 index reaction. Mean IC5 0 values (mM) for inhibition of bupropion hydroxylation were: nelfinavir (2 .5), ritonavir (2.2), and efavirenz (5.5). The reaction was only weakly inh ibited by indinavir, saquinavir, amprenavir, delavirdine, and nevirapine. T he inhibition of bupropion hydroxylation in vitro by nelfinavir, ritonavir, and efavirenz indicates inhibitory potency versus CYP2B6 and suggests the potential for clinical drug interactions.