Lopinavir/ritonavir reduces bupropion plasma concentrations in healthy subjects.
Hogeland GW, Swindells S, McNabb JC, Kashuba AD, Yee GC, Lindley CM.
Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina School of Pharmacy, Chapel Hill, North Carolina, USA.
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) infinity by 57% (90% CI, 32-83%; P<0.01). Hydroxybupropion C(max) and AUC infinity 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.
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PMID: 17186001 [PubMed - indexed for MEDLINE]