Pharmacodynamic evaluation of warfarin and rosuvastatin co-administration in healthy subjects

Eur J Clin Pharmacol. 2005 Oct;61(9):621-5. doi: 10.1007/s00228-005-0986-6. Epub 2005 Oct 19.

Abstract

Objective: To determine whether co-administration of rosuvastatin alters the pharmacodynamics of warfarin, thereby requiring additional monitoring of the anticoagulant effects of warfarin.

Methods: In this open-labeled, placebo-controlled, randomized, two-period, crossover trial with a washout period of 15 days, 12 healthy male volunteers were administered daily oral doses of 5 mg warfarin for 14 days. Either rosuvastatin 40 mg/day (treatment A) or placebo (treatment B) was concomitantly administered on days 8-14. The pharmacodynamic parameters prothrombin time (PT) and international normalized ratio (INR) were evaluated on all 14 days pre-dose during both study periods. On the 8th, 10th, 12th, and 14th days of each study period, PT and INR were also measured at 4 h post-dose of rosuvastatin or placebo. Bleeding time and clotting time were assessed on the 1st, 8th, and 14th days pre-dose.

Results: Data of 10 subjects have been analyzed. No significant effect of rosuvastatin was seen on the steady-state pharmacodynamics of warfarin during concomitant administration.

Conclusion: Rosuvastatin did not significantly alter the anticoagulant effects of warfarin in this study.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Anticoagulants / administration & dosage
  • Anticoagulants / pharmacokinetics*
  • Blood Coagulation / drug effects
  • Cross-Over Studies
  • Drug Interactions
  • Drug Therapy, Combination
  • Fluorobenzenes / pharmacology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • International Normalized Ratio
  • Male
  • Prothrombin Time
  • Pyrimidines / pharmacology*
  • Rosuvastatin Calcium
  • Sulfonamides / pharmacology*
  • Warfarin / administration & dosage
  • Warfarin / pharmacokinetics*

Substances

  • Anticoagulants
  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrimidines
  • Sulfonamides
  • Warfarin
  • Rosuvastatin Calcium