Effect of rifampicin on pravastatin pharmacokinetics in healthy subjects

Abstract

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 1 2 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-∞)] 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-∞) 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.