Effect of rifampicin on pravastatin pharmacokinetics in healthy subjects

Br J Clin Pharmacol. 2004 Feb;57(2):181-7. doi: 10.1046/j.1365-2125.2003.01972.x.


Aims: Previous work has shown that rifampicin, a potent inducer of several cytochrome P450 (CYP) enzymes and transporters, decreased the plasma concentrations of simvastatin acid by more than 90%. This study was conducted to investigate the effect of rifampicin on the pharmacokinetics of pravastatin.

Methods: In a randomised, cross-over two-phase study with a washout of 4 weeks, 10 healthy volunteers received a 5-day pretreatment with rifampicin (600 mg daily) or placebo. On day 6, a single 40 mg dose of pravastatin was administered orally. Plasma concentrations of pravastatin were measured up to 12 h by a sensitive LC-MS-MS method.

Results: During the rifampicin phase, the mean total area under the plasma concentration-time curve of pravastatin [AUC(0-infinity )] was 69% (range 24-220%) of the corresponding value during the placebo phase (P < 0.05, 95% confidence interval for the difference -51.9 - -0.4 ng ml-1.h). In five of the 10 subjects the AUC(0-infinity ) of pravastatin during the rifampicin phase was 50% or less of that during the placebo phase. Rifampicin had no significant effect on the peak concentration, elimination half-life or renal clearance of pravastatin.

Conclusions: Rifampicin caused a statistically significant decrease in the plasma concentration of pravastatin given as a single oral dose to healthy subjects. However, the effect of rifampicin varied greatly between subjects. The mean rifampicin-induced decrease in pravastatin concentration was considerably smaller than that observed previously for simvastatin.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Area Under Curve
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics*
  • Plasma
  • Pravastatin / administration & dosage
  • Pravastatin / blood
  • Pravastatin / pharmacokinetics*
  • Rifampin / administration & dosage
  • Rifampin / pharmacology*


  • Enzyme Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pravastatin
  • Rifampin