Lopinavir/ritonavir reduces bupropion plasma concentrations in healthy subjects

G. W. Hogeland, Susan Swindells, J. C. McNabb, A. D M Kashuba, Gary C Yee, C. M. Lindley

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Abstract

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 (Cmax) 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 Cmax 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.

Original languageEnglish (US)
Pages (from-to)69-75
Number of pages7
JournalClinical Pharmacology and Therapeutics
Volume81
Issue number1
DOIs
StatePublished - Jan 1 2007

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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