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Ritonavir Has Minimal Impact on the Pharmacokinetic Disposition of a Single Dose of Bupropion Administered to Human Volunteers

From the Molecular Pharmacogenetics Laboratory (Dr Hesse, Dr Court) and the Clinical Pharmacology Laboratory (Dr Greenblatt, Dr von Moltke), Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts.

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.

Key Words: Bupropion • ritonavir • pharmacokinetics • drug-drug interaction

Address for reprints: Michael H. Court, Tufts University School of Medicine, Molecular Pharmacogenetics Laboratory, Department of Pharmacology and Experimental Therapeutics, 136 Harrison Avenue, Boston, MA 02111; e-mail: michael.court{at}tufts.edu.

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