Pharmacokinetic interaction between nelfinavir and pravastatin in HIV-seronegative volunteers: ACTG Study A5108

AIDS. 2006 Mar 21;20(5):725-9. doi: 10.1097/01.aids.0000216373.53819.92.


Background: Nelfinavir, an HIV protease inhibitor with numerous drug-drug interactions, is associated with dyslipidemia. Pravastatin is the preferred statin prescribed for HIV-associated dyslipidemia.

Objective: To examine the effect of nelfinavir on pravastatin pharmacokinetics.

Design: Open-label study in healthy HIV-seronegative adults conducted at the AIDS Clinical Trials Group sites in the United States.

Methods: Subjects received pravastatin 40 mg daily and underwent intensive sampling for pharmacokinetics on day 3. Subjects took only nelfinavir 1250 mg twice daily on days 4-12. On days 13-15, subjects continued nelfinavir and reinitiated pravastatin. Plasma samples were collected over 24 h for the calculation of pravastatin area under the concentration-time curve for 0-24 h on days 3 and 16.

Results: Data from 14 subjects with complete pharmacokinetic samples were available for analysis. The median within-subject percentage change in pravastatin AUC was a decrease of 46.5%. Pravastatin maximum plasma concentrations were also lower when pravastatin was administered with nelfinavir. Median values for the maximum plasma concentrations were 27.9 and 12.4 ng/ml for days 3 and 16, respectively, and the median within-subject decrease was 40.1%.

Conclusions: Coadministration of pravastatin and nelfinavir led to a substantial reduction in pravastatin plasma concentrations. Higher doses of pravastatin may need to be prescribed in order to achieve optimal lipid-lowering activity.

Publication types

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

MeSH terms

  • Adult
  • Area Under Curve
  • Drug Administration Schedule
  • Drug Interactions
  • Female
  • HIV Protease Inhibitors / blood
  • HIV Protease Inhibitors / pharmacokinetics*
  • HIV Seronegativity
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / blood
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics*
  • Male
  • Nelfinavir / blood
  • Nelfinavir / pharmacokinetics*
  • Pravastatin / blood
  • Pravastatin / pharmacokinetics*
  • Time Factors
  • Volunteers


  • HIV Protease Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Nelfinavir
  • Pravastatin