Reduction in the plasma clearance rate of warfarin induced by cimetidine

The interaction between the histamine H-2 receptor antagonist, cimetidine, and warfarin sodium was prospectively studied in 14 patients who were previously anticoagulated for five years. The patients received warfarin and cimetidine concomitantly for a minimum of ten days. Seven of the patients experienced increases in plasma warfarin concentrations. This correspondingly resulted in abnormal prolongation of their prothrombin times. In these patients the elevation in the steady-state warfarin concentration demonstrates that coadministration of cimetidine significantly reduces the plasma clearance rate of warfarin. The serum and urine metabolite levels of warfarin were not qualitatively different in the absence in contrast to the presence of cimetidine. It is apparent that cimetidine can act as an inhibitory influence on the catabolic degradation of warfarin.