Dose-related reduction in bupropion plasma concentrations by ritonavir

J Clin Pharmacol. 2010 Oct;50(10):1180-7. doi: 10.1177/0091270009359524. Epub 2010 May 19.

Abstract

The effect of repeat oral doses of ritonavir, at high (600 mg twice daily) and low (100 mg twice daily) doses, on the pharmacokinetics of a single dose of bupropion was evaluated in healthy volunteers. Subjects received a single dose of 150 mg of bupropion on day 1 and twice-daily ritonavir from day 8 through day 30. Ritonavir was up-titrated from 300 mg twice daily to 600 mg twice daily in the high-dose ritonavir study, whereas subjects remained on 100 mg twice-daily ritonavir in low-dose ritonavir study. Subjects received a second single dose of bupropion on day 24. Serial blood samples were obtained to evaluate the pharmacokinetics of bupropion and its metabolites on days 1 and 24. Steady-state ritonavir led to a decrease of area under the curve and maximum plasma concentration of bupropion by 62% to 67% in the high-dose study and by 21% to 22% in the low-dose study, indicating a drug interaction of statistical and clinical significance, particularly at high doses of ritonavir. These studies demonstrate that the reduction of bupropion exposure by ritonavir is dose-related. Dosage adjustment of bupropion may be needed when administered with ritonavir. However, the maximum recommended daily dose of bupropion should not be exceeded.

MeSH terms

  • Adult
  • Antidepressive Agents, Second-Generation / administration & dosage
  • Antidepressive Agents, Second-Generation / blood
  • Antidepressive Agents, Second-Generation / pharmacokinetics*
  • Area Under Curve
  • Bupropion / administration & dosage
  • Bupropion / blood
  • Bupropion / pharmacokinetics*
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Female
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / pharmacokinetics*
  • Half-Life
  • Humans
  • Male
  • Middle Aged
  • Ritonavir / administration & dosage
  • Ritonavir / pharmacokinetics*

Substances

  • Antidepressive Agents, Second-Generation
  • Delayed-Action Preparations
  • HIV Protease Inhibitors
  • Bupropion
  • Ritonavir