title: Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: potential drug interactions with bupropion.
abstract: Since antiretroviral drugs are known to inhibit many cytochrome P450 isoforms, the inhibition of CYP2B6 by non-nucleoside reverse transcriptase inhibitors and viral protease inhibitors was studied in vitro in human liver microsomes using bupropion hydroxylation as the CYP2B6 index reaction. Mean IC(50) values (microM) for inhibition of bupropion hydroxylation were: nelfinavir (2.5), ritonavir (2.2), and efavirenz (5.5). The reaction was only weakly inhibited by indinavir, saquinavir, amprenavir, delavirdine, and nevirapine. The inhibition of bupropion hydroxylation in vitro by nelfinavir, ritonavir, and efavirenz indicates inhibitory potency versus CYP2B6 and suggests the potential for clinical drug interactions.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Ave., Boston, Massachusetts, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Hesse
authors.forename: L L
authors.initials: LL
authors.lastname: von Moltke
authors.forename: R I
authors.initials: RI
authors.lastname: Shader
authors.forename: D J
authors.initials: DJ
authors.lastname: Greenblatt
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000378:metabolism* / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases; D048588:Benzoxazines; D016642:Bupropion / Q000378:metabolism* / Q000494:pharmacology; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D006900:Hydroxylation; D020128:Inhibitory Concentration 50; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D019888:Nelfinavir / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D019438:Ritonavir / Q000494:pharmacology
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D018687:Antidepressive Agents, Second-Generation; D048588:Benzoxazines; D003521:Cyclopropanes; D065607:Cytochrome P-450 Enzyme Inhibitors; D017320:HIV Protease Inhibitors; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; D016642:Bupropion; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; D019888:Nelfinavir; C098320:efavirenz; D019438:Ritonavir