Interaction of chronic daily warfarin therapy and rifampin

To evaluate the interaction between the antibiotic rifampin and the anticoagulant warfarin during chronic therapy, eight normal subjects were given daily doses of warfarin for 21 days to achieve therapeutic hypoprothrombinemia. Daily blood samples were analyzed for one-stage prothrombin activity and for warfarin content spectrophotometrically and chromatographically. One month later, the same warfarin dose was repeated plus rifampin, 600 mg a day orally. For the last 10 days of every experiment, there was a highly significant lessening of both the hypoprothrombinemic effect (P less than 0.001) and the blood levels of warfarin (P less than 0.001). No significant difference in the warfarin levels was found between the spectrophotometric and chromatographic methods. It is concluded that rifampin markedly decreases the hypoprothrombinemic effect of warfarin during long-term therapy by enhancing its elimination from plasma. This conclusion was reinforced by finding increased amounts of warfarin metabolites in urine and stool.