Lopinavir/ritonavir Reduces Bupropion Plasma Concentrations in Healthy Subjects

Limited data are available about the effect of steady‐state lopinavir and ritonavir (LPV/r) on bupropion pharmacokinetics. As patients may benefit by using these two agents in combination, this study determined the extent and direction of this drug–drug interaction. Twelve healthy volunteers received a single 100 mg dose of sustained‐release bupropion before and after 2 weeks of treatment with LPV/r 400 mg/100 mg twice daily. Pharmacokinetics profiles were determined on days 1 and 30 for bupropion and hydroxybupropion and days 29 and 30 for LPV/r. LPV/r administration significantly decreased bupropion maximum plasma concentration ( C max ) by 57% (90% confidence interval (CI), 38–76% P <0.01) and area under the curve (AUC) ∞ by 57% (90% CI, 32–83% P <0.01). Hydroxybupropion C max and AUC ∞ decreased by 31% (90% CI, 7–55% P <0.01) and by 50% (90% CI, 34–65% P <0.01), respectively. No significant changes in the pharmacokinetics of LPV/r were found following administration of a single dose of bupropion. Concurrent use of LPV/r and bupropion resulted in decreased exposure to bupropion and its active metabolite hydroxybupropion that may necessitate as much as a 100% dose increase of bupropion. A probable mechanism for this interaction is the concurrent induction of cytochrome P450 2B6 and UDP‐glucuronosyltransferase enzymes. LPV/r exposure is unaffected by a single dose of bupropion. Clinical Pharmacology & Therapeutics (2007) 81 , 69–75. doi: 10.1038/sj.clpt.6100027