Enhanced elimination of warfarin during treatment with cholestyramine

1 The elimination and anticoagulant activity of a single intravenous dose of warfarin (1.0-1.2 mg/kg) without and with concomitant cholestyramine treatment (about 4 g three times daily) was studied in five healthy male subjects. 2 Cholestyramine treatment decreased the biological half-life of plasma warfarin (from a mean value of 2 days -1.3 days) and increased the total clearance of this drug (from a mean value of 37 ml kg-1 day-1--53 ml kg--1 day--1). 3 The total anticoagulant effect per dose of warfarin, as measured by the area under the effect v time curve, was also reduced by cholestyramine (average reduction of about 25%). 4 Warfarin possibly undergoes enterohepatic recycling in man which can be interrupted by cholestyramine.