EFFECTS OF DX-9065A, AN ORALLY-ACTIVE, NEWLY SYNTHESIZED AND SPECIFICINHIBITOR OF FACTOR XA, AGAINST 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 two kin ds of experimental disseminated intravascular coagulation (DIC) in rat s. Endotoxin-induced experimental DIC was induced by a 4-h sustained i nfusion of endotoxin at a dose of 100 mg/kg. Thromboplastin-induced ex perimental DIC was induced by a bolus injection of thromboplastin at a dose of 150 mg/kg. The rats were orally administered DX-9065a at 10, 30 or 100 mg/kg 30 min before endotoxin or thromboplastin injection. I n both DIC models, DX-9065a showed a protective effect against DIC, at all doses and in all parameters, including fibrin/fibrinogen degradat ion products (FDP), fibrinogen level, prothrombin time, activated part ial thromboplastin time, platelet count and the number of renal glomer uli with fibrin thrombi. When DX-9065a was orally administrated at 100 mg/kg without endotoxin or thromboplastin, no significant changes wer e seen in hemostatic parameters except PT and APTT, and no fibrin thro mbi or abnormal bleeding were seen in renal specimens. These findings suggest that the new oral anti-Xa drug, DX-9065a, has an effect in red ucing the severity of DIC. However, further dose-finding acid safety s tudies of this drug have still to be assessed.