Journal
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
Volume 57, Issue 2, Pages 181-187Publisher
WILEY
DOI: 10.1046/j.1365-2125.2003.01972.x
Keywords
interaction; pravastatin; rifampicin
Categories
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available