Key result
Pretreatment with clopidogrel or ticlopidine significantly reduced the AUC of hydroxybupropion by 52% (P=0.001) and 84% (P<0.0001), respectively, indicating CYP2B6 inhibition.
Why the study?
Does clopidogrel or ticlopidine reduce CYP2B6-catalyzed bupropion hydroxylation in healthy male volunteers?
Does clopidogrel or ticlopidine reduce CYP2B6-catalyzed bupropion hydroxylation in healthy male volunteers?
Both clopidogrel and ticlopidine significantly inhibit CYP2B6-catalyzed bupropion hydroxylation, indicating a potential for drug-drug interactions requiring dose adjustments.
May warrant bupropion dose caution with thienopyridines; leaves open validation in patient populations.
OBJECTIVE: Our objective was to study the effect of the antiplatelet agents clopidogrel and ticlopidine on bupropion (INN, amfebutamone) hydroxylation, a probe reaction for cytochrome P450 (CYP) 2B6 activity. METHODS: Twelve healthy male volunteers took a single 150-mg oral dose of bupropion either alone or after pretreatment with 75 mg clopidogrel once daily or 250 mg ticlopidine twice daily for 4 days. On day 4, a single 150-mg oral dose of bupropion was administered. Plasma concentrations of bupropion and its CYP2B6-catalyzed metabolite, hydroxybupropion, were measured for up to 72 hours. RESULTS: The mean area under the plasma concentration-time curve (AUC) of hydroxybupropion calculated from time 0 to infinity was reduced by 52% ( P = .001; 95% confidence interval [CI], 39% to 66%) by clopidogrel and by 84% ( P < .0001; 95% CI, 73% to 94%) by ticlopidine. Clopidogrel reduced the AUC ratio of hydroxybupropion over bupropion by 68% ( P = .002; 95% CI, 58% to 77%) and ticlopidine by 90% ( P = .001; 95% CI, 85% to 96%). The AUC of bupropion was increased by 60% ( P = .02; 95% CI, 21% to 98%) and by 85% ( P < .0001; 95% CI, 48% to 85%) with clopidogrel and ticlopidine, respectively. CONCLUSIONS: Both clopidogrel and ticlopidine significantly inhibited the CYP2B6-catalyzed bupropion hydroxylation. Patients receiving either clopidogrel or ticlopidine are likely to require dose adjustments when treated with drugs primarily metabolized by CYP2B6.
No takes yet. Share an insight, caveat, or question.
Turpeinen et al. (2005) studied Healthy volunteers (n=12). Clopidogrel and ticlopidine vs. Bupropion alone was evaluated on Mean area under the plasma concentration-time curve (AUC) of hydroxybupropion from time 0 to infinity (52% reduction (clopidogrel), 84% reduction (ticlopidine), 95% CI 39% to 66% (clopidogrel), 73% to 94% (ticlopidine), p=.001 (clopidogrel), <.0001 (ticlopidine)). Pretreatment with clopidogrel or ticlopidine significantly reduced the AUC of hydroxybupropion by 52% (P=0.001) and 84% (P<0.0001), respectively, indicating CYP2B6 inhibition.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: