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/
Source: PubMed


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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Available from: David Adson, Oct 20, 2015
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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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    ABSTRACT: 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a popular recreational drug. The study aim was to explore the role of dopamine in the psychotropic effects of MDMA using bupropion to inhibit the dopamine and norepinephrine transporters through which MDMA releases dopamine and norepinephrine. The present study investigated the pharmacodynamic and pharmacokinetic interactions between bupropion and MDMA in 16 healthy subjects using a double-blind, placebo-controlled, crossover design. Bupropion reduced the MDMA-induced elevations in plasma norepinephrine concentrations and the heart rate response to MDMA. In contrast, bupropion increased plasma MDMA concentrations and prolonged its subjective effects. Conversely, MDMA increased plasma bupropion concentrations. The results indicate a role for the transporter-mediated release of norepinephrine in the cardiostimulant effects of MDMA but do not support a modulatory role for dopamine in the mood effects of MDMA. These results also indicate that the use of MDMA during therapy with bupropion may result in higher plasma concentrations of both MDMA and bupropion and enhanced mood effects but lower cardiac stimulation. The American Society for Pharmacology and Experimental Therapeutics.
    Journal of Pharmacology and Experimental Therapeutics 02/2015; 353(1). DOI:10.1124/jpet.114.222356 · 3.97 Impact Factor
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    • "Bupropion acts predominantly on 2D6 and has no action on 2C9.[22] This makes the bupropion-warfarin interaction, in this case, difficult to explain in the light of available evidence. "
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    ABSTRACT: Depressive illness and thromboembolic disorders are both highly prevalent. Warfarin is frequently combined with an antidepressant drug, the choice of which depends mainly on the risk of a hemorrhagic complication. Patients requiring the warfarin are often in the older age group, where the newer antidepressants with a better safety profile are preferred over tricyclic antidepressants. We report herein, a patient who was on bupropion for depression, when he developed deep vein thrombosis high-risk. Warfarin was started. While on this combination bupropion was abruptly stopped. This caused a more than two-fold elevation of international normalized ratio (INR) above the level, which is considered a high-risk for a hemorrhagic complication. INR reverted back to the desired level on reintroduction of bupropion. This indicates that a bupropion-warfarin combination should be used with the caution, though there has been no reported interaction so far.
    Indian Journal of Psychological Medicine 07/2013; 35(3):311-3. DOI:10.4103/0253-7176.119488
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    • "When these medications are co-administered with tamoxifen to women with an EM phenotype, endoxifen concentrations are similar to those observed in PM and have the potential, therefore, to reduce tamoxifen efficacy [9,43,44]. Other commonly used medications such as buproprion, duloxetine, clomipramine, thioridazine, pherphenazine, and pimozide exhibit inhibition close to that of paroxetine, fluoxetine and quinidine [44-46]. While we found that some women did change their co-medications, this was unrelated to CYP2D6 genotype. "
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    ABSTRACT: Pharmacogenetic testing holds major promise in allowing physicians to tailor therapy to patients based on genotype. However, there is little data on the impact of pharmacogenetic test results on patient and clinician choice of therapy. CYP2D6 testing among tamoxifen users offers a potential test case of the use of pharmacogenetic testing in the clinic. We evaluated the effect of CYP2D6 testing in clinical practice to determine whether genotype results affected choice of hormone therapy in a prospective cohort study. Women planning to take or currently taking tamoxifen were considered eligible. Participants were enrolled in an informational session that reviewed the results of studies of CYP2D6 genotype on breast cancer recurrence. CYP2D6 genotyping was offered to participants using the AmpliChip CYP450 Test. Women were classified as either poor, intermediate, extensive or ultra-rapid metabolizers. Results were provided to clinicians without specific treatment recommendations. Follow-up was performed with a structured phone interview 3 to 6 months after testing to evaluate changes in medication. A total of 245 women were tested and 235 completed the follow-up survey. Six of 13 (46%) women classified as poor metabolizers reported changing treatment compared with 11 of 218 (5%) classified as intermediate, extensive or ultra-rapid metabolizers (P < 0.001). There was no difference in treatment choices between women classified as intermediate and extensive metabolizers. In multi-variate models that adjusted for age, race/ethnicity, educational status, method of referral into the study, prior knowledge of CYP2D6 testing, the patients' CYP2D6 genotype was the only significant factor that predicted a change in therapy (odds ratio 22.8; 95% confidence interval 5.2 to 98.8). Genetic testing did not affect use of co-medications that interact with CYP2D6. CYP2D6 genotype testing led to changes in therapy among poor metabolizers, even in the absence of definitive data that an alternative medicine improved outcomes. Pharmacogenetic testing can affect choice of therapy, even in the absence of definitive data on clinical impact.
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