alexa Effect of rifampicin on pravastatin pharmacokinetics in healthy subjects.
Business & Management

Business & Management

Journal of Business & Financial Affairs

Author(s): Kyrklund C, Backman JT, Neuvonen M, Neuvonen PJ

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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-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.
This article was published in Br J Clin Pharmacol and referenced in Journal of Business & Financial Affairs

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