PROTECTIVE EFFECTS OF DX-9065A, AN ORALLY-ACTIVE, NOVEL SYNTHESIZED AND SELECTIVE INHIBITOR OF FACTOR XA, AGAINST THROMBOPLASTIN-INDUCED EXPERIMENTAL DISSEMINATED INTRAVASCULAR COAGULATION IN RATS

We investigated the protective effects of DX-9065a, an orally active, newly synthesized, and specific inhibitor of factor Xa, against experi mental disseminated intravascular coagulation (DIC) in rats. Experimen tal DIC was induced by a 4 hour sustained infusion of thromboplastin a t a dose of 2.5 mg/kg. The rats were orally administered DX-9065a at 1 0, 30, 100 mg/kg 30 minutes before thromboplastin injection. In this D IC model, DX-9065a showed a protective effect against DIC, at all dose s and in all parameters, including fibrin(ogen) degradation products, fibrinogen level, thrombin-antithrombin III complex level, prothrombin time (PT), activated partial thromboplastin time (APTT), platelet cou nt, and the number of renal glomeruli with fibrin thrombi. When DX-906 5a was orally administered at 100 mg/kg without thromboplastin, no sig nificant changes were seen in hemostatic parameters except PT and APTT , and no fibrin thrombi or abnormal bleeding were seen in renal specim ens. These findings suggested that the new oral anti-Xa drug, DX-9065a , has a protective effect against thromboplastin-induced DIC model wit h little risk of bleeding.