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

Abstract

To determine whether co-administration of rosuvastatin alters the pharmacodynamics of warfarin, thereby requiring additional monitoring of the anticoagulant effects of warfarin. 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. Data of 10 subjects have been analyzed. No significant effect of rosuvastatin was seen on the steady-state pharmacodynamics of warfarin during concomitant administration. Rosuvastatin did not significantly alter the anticoagulant effects of warfarin in this study.