Ritonavir has minimal impact on the pharmacokinetic disposition of a single dose of Bupropion administered to human volunteers

A drug-drug interaction study was conducted to determine whether ritonavir (200 mg; 4 doses over 2 days) alters the pharmacokinetic disposition of bupropion (75 mg; once) coadministered to 7 healthy Volunteers in a placebo-controlled 2-way crossover study. Serum samples collected from 0 to 24 hours after bapropion administration were assayed for concentrations of bupropion and metabolites (hydroxybupropion, threohydrobupropion, and erythrohydrobupropion). Derived pharmacokinetic parameters were compared between placebo/bupropion and ritonavir/bupropion trials by paired t test. The effect of ritonavir on most pharmacokinetic parameters was minimal (< 20% mean change). The only parameters that showed a statistically significant effect were threohydrobupropion area under the blood concentration curve (14% +/- 5% decrease, mean +/- SE; P =.04) and erythrohydrobupropion time-to-maximal serum concentration (161% +/- 92% increase, P =.03), suggesting that ritonavir may inhibit the carbonyl reductose enzyme responsible for formation of these metabolites. These findings indicate that short-term ritonavir dosing has only minimal impact on the pharmacokinetic disposition of a single dose of bupropion in healthy volunteers.