Bupropion plasma levels and CYP2D6 phenotype

Ther Drug Monit. 1996 Oct;18(5):581-5. doi: 10.1097/00007691-199610000-00010.

Abstract

All available antidepressants with the exception of fluvoxamine and nefazodone either are metabolized by cytochrome P450 2D6 (CYP2D6) and/or inhibit this isozyme. To date, nothing in this regard has been published concerning bupropion. We report that plasma level/dose ratios for bupropion, and its metabolites erythrohydrobupropion and threohydrobupropion, were not associated with debrisoquine metabolic status in 12 patients, three of whom were poor 2D6 metabolizers. The plasma level/dose ratios for the metabolite hydroxybupropion were, however, significantly higher in poor 2D6 metabolizers. In three patients, who received a second phenotyping test during treatment with bupropion, debrisoquine metabolic ratios were not increased. It is thus inferred that bupropion is neither metabolized by nor inhibits CYP2D6. The potential accumulation of hydroxybupropion after CYP2D6 inhibition may, however, contribute to toxicity and impair bupropion's therapeutic effectiveness.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Antidepressive Agents, Second-Generation / blood*
  • Bupropion / administration & dosage
  • Bupropion / adverse effects
  • Bupropion / blood*
  • Cytochrome P-450 CYP2D6 / genetics*
  • Depressive Disorder / blood*
  • Depressive Disorder / drug therapy
  • Depressive Disorder / enzymology*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Phenotype
  • Seizures / chemically induced

Substances

  • Antidepressive Agents, Second-Generation
  • Bupropion
  • Cytochrome P-450 CYP2D6