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 bupropion 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 reductase 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.
Hesse
Leah M
LM
Molecular Pharmacogenetics Laboratory, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA.
Greenblatt
David J
DJ
von Moltke
Lisa L
LL
Court
Michael H
MH
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000493:pharmacokinetics*; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics*; D016642:Bupropion / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions; D006801:Humans; D008297:Male; D019438:Ritonavir / Q000097:blood / Q000493:pharmacokinetics*
D018687:Antidepressive Agents, Second-Generation; D000998:Antiviral Agents; C496216:hydrobupropion; D016642:Bupropion; D019438:Ritonavir; C496215:radafaxine