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Inhibition of CYP2D6 Activity by Bupropion

Kotlyar, Michael PharmD*†; Brauer, Lisa H. PhD; Tracy, Timothy S. PhD*; Hatsukami, Dorothy K. PhD; Harris, Jennifer BS; Bronars, Carrie A. MA; Adson, David E. MD

Journal of Clinical Psychopharmacology: June 2005 - Volume 25 - Issue 3 - p 226-229
doi: 10.1097/01.jcp.0000162805.46453.e3
Original Contributions

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.

*Department of Experimental and Clinical Pharmacology, College of Pharmacy, †Department of Psychiatry, and ‡Transdisciplinary Tobacco Use Research Center, University of Minnesota, Twin Cities Campus, Minneapolis, MN.

Received August 10, 2004; accepted after revision February 10, 2005.

Supported by University of Minnesota Academic Health Center Faculty Research Development grant no. 01-01 and grant no. M01-RR00400 from the General Clinical Research Centers program of the National Center for Research Resources.

Address correspondence and reprint requests to Michael Kotlyar, PharmD, Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 7-170 Weaver Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455. E-mail: kotly001@umn.edu.

© 2005 Lippincott Williams & Wilkins, Inc.