Protective effects of ONO-3307, a new synthetic protease inhibitor against experimental disseminated intravascular coagulation in rats

The effects of ONO-3307 (4-sulfamoylphenyl 4-guanidinobenzoate methanesulfonate), a new synthetic Protease inhibitor, on endotoxin-induced experimental disseminated intravascular coagulation (DIC) were studied in rats. Experimental DIC was induced by a 4-h sustained infusion of endotoxin at a dose of 100 mg/kg. The rats were infused continuously with ONO-3307 at a dose of 1, 10 or 100 micrograms/kg/h into a femoral vein for 4 h. Simultaneously with the agent infusion, endotoxin (100 mg/kg/4h) was administered into the contralateral femoral vein. A protective effect against DIC was noted in the rats treated with 10 or 100 micrograms/kg/h of ONO-3307 in the following parameters: fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count and the number of renal glomeruli with fibrin thrombi. Therefore, ONO-3307 inhibited the aggravation of endotoxin-induced experimental DIC in rats.