Article

Inhibition of CYP2D6 Activity by Bupropion

Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Twin Cities Campus, Minneapolis, MN 55455, USA.
Journal of Clinical Psychopharmacology (Impact Factor: 3.24). 07/2005; 25(3):226-9. DOI: 10.1097/01.jcp.0000162805.46453.e3
Source: PubMed

ABSTRACT

The purpose of this study was to assess the effect of bupropion on cytochrome P450 2D6 (CYP2D6) activity. Twenty-one subjects completed this repeated-measures study in which dextromethorphan (30-mg oral dose) was administered to smokers at baseline and after 17 days of treatment with either bupropion sustained-release (150 mg twice daily) or matching placebo. Subjects quit smoking 3 days before the second dextromethorphan administration. To assess CYP2D6 activity, urinary dextromethorphan/dextrorphan metabolic ratios were calculated after an 8-hour urine collection. Thirteen subjects received bupropion, and 8 received placebo. In those receiving active medication, the dextromethorphan/dextrorphan ratio increased significantly at the second assessment relative to the first (0.012 +/- 0.012 vs. 0.418 +/- 0.302; P < 0.0004). No such change was observed in those randomized to placebo (0.009 +/- 0.010 vs. 0.017 +/- 0.015; P = NS). At baseline, all subjects were phenotypically extensive CYP2D6 metabolizers (metabolic ratio <0.3); after treatment, 6 of 13 subjects receiving bupropion, but none of those receiving placebo, had metabolic ratios consistent with poor CYP2D6 metabolizers. Bupropion is therefore a potent inhibitor of CYP2D6 activity, and care should be exercised when initiating or discontinuing bupropion use in patients taking drugs metabolized by CYP2D6.

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    • "Bupropion, and particularly erythro-hydrobuprion and threohydrobupropion have previously been shown to inhibit CYP2D6 (Jefferson et al., 2005; Kotlyar et al., 2005; Reese TABLE 3 Pharmacokinetic parameters of MDMA and bupropion and metabolites Values are mean 6 S.E.M. in 16 healthy subjects. "
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    • "Although bupropion is not significantly cleared by CYP2D6, it has been described as a potent inhibitor of this important xenobiotic metabolizing enzyme in vivo (Kotlyar et al. 2005). Bupropion has been shown to alter the clinical PK of CYP2D6 substrates, including dextromethorphan (Kotlyar et al. 2005), nortriptyline (Weintraub 2001), metoprolol (McCollum et al. 2004), venlafaxine (Kennedy et al. 2002) and desipramine (Jefferson et al. 2005; Reese et al. 2008). Further in vitro mechanistic studies demonstrated that neither bupropion nor hydroxybupropion are significant inhibitors of CYP2D6, rather the reductive metabolites are potent competitive inhibitors of CYP2D6 (Reese et al. 2008). "
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