title: Effect of rifampicin on pravastatin pharmacokinetics in healthy subjects.
abstract: OBJECTIVE
  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.affiliation: Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Carl
authors.initials: C
authors.lastname: Kyrklund
authors.forename: Janne T
authors.initials: JT
authors.lastname: Backman
authors.forename: Mikko
authors.initials: M
authors.lastname: Neuvonen
authors.forename: Pertti J
authors.initials: PJ
authors.lastname: Neuvonen
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010949:Plasma; D017035:Pravastatin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin; D012293:Rifampin