Efavirenz induces CYP2B6-mediated hydroxylation of bupropion in healthy subjects

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 49; no. 5; p. 513
• Main Authors: Robertson, Sarah M, Maldarelli, Frank, Natarajan, Ven, Formentini, Elizabeth, Alfaro, Raul M, Penzak, Scott R
• Format: Journal Article
• Language: English
• Published: United States 15.12.2008
• Subjects: Adult; Alkynes; Anti-HIV Agents - blood; Anti-HIV Agents - pharmacology; Antidepressive Agents, Second-Generation - blood; Antidepressive Agents, Second-Generation - pharmacokinetics; Antidepressive Agents, Second-Generation - pharmacology; Aryl Hydrocarbon Hydroxylases - drug effects; Aryl Hydrocarbon Hydroxylases - genetics; Aryl Hydrocarbon Hydroxylases - metabolism; Benzoxazines - administration & dosage; Benzoxazines - blood; Benzoxazines - pharmacokinetics; Benzoxazines - pharmacology; Bupropion - administration & dosage; Bupropion - analogs & derivatives; Bupropion - blood; Bupropion - metabolism; Bupropion - pharmacokinetics; Cyclopropanes; Cytochrome P-450 CYP2B6; Delayed-Action Preparations; Drug Interactions; Enzyme Induction; Female; Genetic Variation; Humans; Hydroxylation - drug effects; Male; Middle Aged; Oxidoreductases, N-Demethylating - drug effects; Oxidoreductases, N-Demethylating - genetics; Oxidoreductases, N-Demethylating - metabolism; Pharmacogenetics; Young Adult
• ISSN: 1525-4135
• DOI: 10.1097/QAI.0b013e318183a425

To characterize the effect of efavirenz on bupropion hydroxylation as a marker of cytochrome P450 (CYP) 2B6 activity in healthy subjects. Thirteen subjects received a single oral dose of bupropion SR 150 mg before and after 2 weeks of efavirenz administration for comparison of bupropion and hydroxybupropion pharmacokinetics. Efavirenz plasma concentrations were also assessed. Subjects were genotyped for CYP2B6 (G516T, C1459T, and A785G), CYP3A4 (A-392G), CYP3A5 (A6986G), and multidrug resistance protein 1 (C3435T). The area under the concentration vs. time curve ratio of hydroxybupropion:bupropion increased 2.3-fold after efavirenz administration (P=0.0001). Bupropion area under the concentration vs. time curve and Cmax decreased by 55% and 34%, respectively (P<0.002). None of the CYP2B6 or CYP3A genotypes evaluated were associated with a difference in bupropion or efavirenz clearance. The 2 individuals homozygous for multidrug resistance protein 1 3435-T/T had 2.5- and 1.8-fold greater bupropion and efavirenz clearance, respectively, relative to C/C and C/T individuals (P<0.05). Our results confirm that efavirenz induces CYP2B6 enzyme activity in vivo, as demonstrated by an increase in bupropion hydroxylation after 2 weeks of efavirenz administration.