Interaction between diflunisal and warfarin

The effect of diflunisal on steady-state warfarin dynamics and kinetics was studied in five healthy men taking daily subtherapeutic doses of warfarin. Diflunisal 500 mg twice daily for 2 wk increased the percentage unbound warfarin from 1.02% to 1.24% and lowered total warfarin from 741 to 533 ng/ml, but did not alter the anticoagulant response (prothrombin complex activity, PCA). When diflunisal was discontinued but warfarin continued, there was a loss of anticoagulant effect and a difference in the rates at which percentage unbound warfarin and total warfarin concentration returned to prediflunisal levels. There was a correlation between plasma diflunisal and percentage unbound warfarin. Diflunisal reduced both the maximum plasma protein-binding capacity for warfarin and the apparent association constant.