Effect of Ubidecarenone on Warfarin Anticoagulation and Pharmacokinetics of Warfarin Enantiomers in Rats

Abstract

Interaction between the antioxidant ubidecarenone and the oral anticoagulant warfarin enantiomers was investigated in rats. The decreased hypoprothrombinemic response, assessed by means of percent changes of prothrombin complex activity and clotting factor VII activity, to warfarin, was observed following oral administration of 1.5 mg/kg racemic warfarin to rats during an 8-day oral regimen (10 mg/kg daily) of ubidecarenone. The antioxidant had no apparent effect on the in vitro rat serum protein binding of warfarin enantiomers. Treatment with ubidecarenone did not affect the absorption and distribution of the S- and R-enantiomers of warfarin, but produced a significant increase in the total serum clearance values of both R- and S-warfarin in rats. This effect was more pronounced with R-warfarin than with S-warfarin. The increased clearance values are attributable to acceleration of certain metabolic pathways and renal excretion of the warfarin enantiomers.