A population approach to study the influence of nevirapine administration on lopinavir pharmacokinetics in HIV-1 infected patients

Eur J Clin Pharmacol. 2005 Apr;61(2):153-6. doi: 10.1007/s00228-005-0900-2. Epub 2005 Mar 11.

Abstract

Objective: The influence of nevirapine (NVP) on lopinavir (LPV) pharmacokinetics was investigated by a population analysis based on a non-linear mixed-effect modelling method.

Methods: In this analysis, 95 HIV-1 infected patients were studied [52 treated with LPV/ritonavir (400/100 mg twice a day) plus nucleoside reverse transcriptase inhibitors (group A), 22 patients treated with LPV/ritonavir (533.3/133.3 mg twice a day) plus NVP (group B) and 21 patients treated with LPV/ritonavir (400/100 mg twice a day) plus NVP (group C)].

Results: The apparent clearance of LPV [mean+/-SD: 4.56+/-3.94 l h(-1) (group A) versus 7.14+/-1.77 l h(-1) (group B) versus 7.74+/-1.45 l h(-1) (group C)] was significantly (P <0.001) increased by the presence of NVP in the antiretroviral regimen and the mean trough plasma concentration of LPV was reduced in group C relative to group A [mean+/-SD: 2.23+/-1.35 mg/l versus 5.29+/-2.19 mg/l (P < 0.001)].

Conclusion: These results suggest an induction of LPV metabolism by NVP.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacokinetics*
  • Bayes Theorem
  • Drug Interactions
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Lopinavir
  • Male
  • Nevirapine / pharmacology*
  • Pyrimidinones / pharmacokinetics*
  • Reverse Transcriptase Inhibitors / pharmacology*

Substances

  • Anti-HIV Agents
  • Pyrimidinones
  • Reverse Transcriptase Inhibitors
  • Lopinavir
  • Nevirapine