Efavirenz induces CYP2B6-mediated hydroxylation of bupropion in healthy subjects

Sarah M. Robertson, Frank Maldarelli, Ven Natarajan, Elizabeth Formentini, Raul M. Alfaro, Scott R. Penzak

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48 Scopus citations

Abstract

Objective: To characterize the effect of efavirenz on bupropion hydroxylation as a marker of cytochrome P450 (CYP) 2B6 activity in healthy subjects. Methods: 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). Results: 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 C max 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 CAT individuals (P < 0.05). Conclusions: 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.

Original languageEnglish
Pages (from-to)513-519
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Volume49
Issue number5
DOIs
StatePublished - 1 Dec 2008

Keywords

  • Bupropion
  • CYP2B6
  • Drug interaction
  • Efavirenz
  • Induction
  • Metabolism

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    Robertson, S. M., Maldarelli, F., Natarajan, V., Formentini, E., Alfaro, R. M., & Penzak, S. R. (2008). Efavirenz induces CYP2B6-mediated hydroxylation of bupropion in healthy subjects. Journal of Acquired Immune Deficiency Syndromes, 49(5), 513-519. https://doi.org/10.1097/QAI.0b013e318183a425