NO PHARMACOKINETIC OR PHARMACODYNAMIC INTERACTION BETWEEN RIVASTATIN AND WARFARIN

Twenty-one healthy, male volunteers completed this double-blind, rando mized, two-period, crossover study to determine the possible pharmacod ynamic and pharmacokinetic interaction of the concomitant administrati on of rivastatin and warfarin sodium in healthy volunteers. The study comprised 2 treatment periods of 8 days each, with a medication-free p eriod of 14 days between the 2 treatment periods. According to the ran domization, the volunteers received either 300 mu g of rivastatin or m atching placebo once daily during the treatment periods. On day 4 of e ach treatment period, the volunteers also received a single oral dose of 25 mg of warfarin sodium together with rivastatin or matching place bo. The effect of rivastatin on both the pharmacokinetics and pharmaco dynamics (prothrombin time and clotting factor VII activity) of warfar in sodium, and the effect of warfarin sodium on the pharmacokinetics o f rivastatin were investigated. Blood sample assays included the analy sis of both R- and S-warfarin, because it is known that the enantiomer s differ in anticoagulant potency. The study results indicate that the concomitant administration of rivastatin and warfarin does not affect the pharmacokinetics of R- and S-warfarin, or the pharmacodynamics of warfarin. Furthermore, the administration of warfarin sodium does not affect the pharmacokinetics of rivastatin.