[Vitamin K deficiency syndrome caused by antituberculous agents]

Vitamin K deficiency caused by antituberculous agents was examined in clinical patients and in experimental rats. When antituberculous agents given to the patients who had only total elental diet because of small intestinal dysfunction, a marked increase in plasma PIVKA-II and a decrease in thrombo-test value were observed. These changes were quickly normalized by administration of vitamin K, despite of succeeding or stopping of antituberculous agents. In rat experiments, effects of four agents (ethambutol, isoniazid, paraaminosalicylate, and rifampicin) on prothrombin time were studied. Among these agents, only rifampicin prolonged prothrombin time. This prolongation depended on drug doses and duration of administration. In addition to this hypoprothrombinemia, an increase in plasma PIVKA-II was also observed, and these changes were normalized within 24 hours of vitamin K administration. These data suggest that rifampicin inhibits vitamin K epoxide reductase interfering re-use of vitamin K and caused vitamin K deficiency in patients with total elental diet.