Effect of plasma protein binding on the anticoagulant action of warfarin in rats.

The relationships between the anticoagulant effect and the concentrations of free and total (sum of free and protein-bound) warfarin in plasma were determined in rats following intravenous administration of single doses of racemic warfarin or S(-)-warfarin. The concentration of total warfarin required to elicit a defined anticoagulant effect varied widely between animals while the concentration of free warfarin showed much less variation. This indicates that the anticoagulant effect of warfarin is a function of its free concentration in plasma.