Efavirenz induces CYP2B6-mediated hydroxylation of bupropion in healthy subjects

J Acquir Immune Defic Syndr. 2008 Dec 15;49(5):513-9. doi: 10.1097/QAI.0b013e318183a425.

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 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).

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Alkynes
  • Anti-HIV Agents
  • Antidepressive Agents, Second-Generation
  • Benzoxazines
  • Cyclopropanes
  • Delayed-Action Preparations
  • Bupropion
  • Aryl Hydrocarbon Hydroxylases
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2B6
  • Oxidoreductases, N-Demethylating
  • efavirenz
  • radafaxine