Lopinavir/ritonavir reduces bupropion plasma concentrations in healthy subjects

Clin Pharmacol Ther. 2007 Jan;81(1):69-75. doi: 10.1038/sj.clpt.6100027.


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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents, Second-Generation / blood
  • Antidepressive Agents, Second-Generation / pharmacokinetics*
  • Area Under Curve
  • Bupropion / analogs & derivatives
  • Bupropion / blood
  • Bupropion / pharmacokinetics*
  • Drug Antagonism
  • Drug Combinations
  • Female
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / pharmacology*
  • Half-Life
  • Humans
  • Lopinavir
  • Male
  • Metabolic Clearance Rate
  • Pyrimidinones / administration & dosage
  • Pyrimidinones / pharmacology*
  • Ritonavir / administration & dosage
  • Ritonavir / pharmacology*


  • Antidepressive Agents, Second-Generation
  • Drug Combinations
  • HIV Protease Inhibitors
  • Pyrimidinones
  • Bupropion
  • Lopinavir
  • Ritonavir
  • radafaxine