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Efavirenz Induces CYP2B6-Mediated Hydroxylation of Bupropion in Healthy Subjects

  1. Author:
    Robertson, S. M.
    Maldarelli, F.
    Natarajan, V.
    Formentini, E.
    Alfaro, R. M.
    Penzak, S. R.

  2. Author Address

    Robertson, Sarah M.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Maldarelli, Frank] Natl Canc Inst, HIV Drug Resistance Program, Frederick, MD USA. [Natarajan, Ven] Natl Canc Inst, SAIC Frederick, Mol Cell Biol Lab, Frederick, MD USA. [Formentini, Elizabeth] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Alfaro, Raul M.; Penzak, Scott R.] NIH, Clin Res Ctr, Dept Pharm, Bethesda, MD 20892 USA.
    1. Year: 2008
  2. Journal: Jaids-Journal of Acquired Immune Deficiency Syndromes
    1. 49
    2. 5
    3. Pages: 513-519
  4. Type of Article: Article
  1. Abstract:

    Objective: To characterize the effect of efavirenz on bupropion hydroxylation as a marker of cytochrome P450 (CYP) 2136 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 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.

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External Sources

  1. PMID: 18989234

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