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Ritonavir Has Minimal Impact on the Pharmacokinetic Disposition of a Single Dose of Bupropion Administered to Human Volunteers
Author(s) -
Hesse Leah M.,
Greenblatt David J.,
Moltke Lisa L.,
Court Michael H.
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006286981
Subject(s) - bupropion , pharmacokinetics , ritonavir , pharmacology , crossover study , placebo , medicine , drug interaction , dosing , oral administration , human immunodeficiency virus (hiv) , immunology , alternative medicine , pathology , antiretroviral therapy , smoking cessation , viral load
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 .