Effect of rifampicin on pravastatin pharmacokinetics in healthy subjects

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–∞)] was 69% (range 24–220%) of the corresponding value during the placebo phase (P