BUPROPION PLASMA-LEVELS AND CYP2D6 PHENOTYPE

All available antidepressants with the exception of fluvoxamine and ne fazodone either are metabolized by cytochrome P450 2D6 (CYP2D6) and/or inhibit this isozyme. To date, nothing in this regard has been publis hed concerning bupropion. We report that plasma level/dose ratios for bupropion, and its metabolites erythrohydrobupropion and threohydrobup ropion, were not associated with debrisoquine metabolic status in 12 p atients, three of whom were poor 2D6 metabolizers. The plasma levelido se ratios for the metabolite hydroxybupropion were, however, significa ntly higher in poor 2D6 metabolizers. In three patients, who received a second phenotyping test during treatment with bupropion, debrisoquin e metabolic ratios were not increased. It is thus inferred that buprop ion is neither metabolized by nor inhibits CYP2D6. The potential accum ulation of hydroxybupropion after CYP2D6 inhibition may, however, cont ribute to toxicity and impair bupropion's therapeutic effectiveness.