Comparative pharmacokinetics of coumarin anticoagulants XXV: Warfarin-ibuprofen interaction in rats

Abstract

The effect of ibuprofen on the pharmacokinetics and anticoagulant action of racemic warfarin was determined in a crossover study on male Sprague-Dawley rats. At average plasma concentrations of 24-83 mg/liter, ibuprofen decreased the biological half-life and increased the total clearance of warfarin. It also increased the anticoagulant effect produced by a given plasma concentration of total (free and protein-bound) warfarin. These effects of ibuprofen appear to be a consequence of its displacing effect on warfarin in plasma.