Effect of rifampicin on pravastatin pharmacokinetics in healthy subjects

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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 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 < 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.