Effects of ONO-3307, a new synthetic protease inhibitor on endotoxin-induced 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 4 hour sustained infusion of endotoxin at a dose of 100mg/kg. The rats were infused continuously with ONO-3307 at 1, 10, 100μg/kg/h into a femoral vein for 4 hour. Simultaneously with the agent infusion, endotoxin was administered into the contralateral femoral vein. A protective effect against DIC was noted in the rats treated with 10 or 100μg/kg/h of ONO-3307 in the following parameters: fibrinogen and fibrin degradation products, platelet count, fibrinogen level, prothrombin time, partial thromboplastin time and the number of renal glomeruli with fibrin thrombi. These results demonstrated that ONO-3307 reduces the extent of changes of the coagulation parameters caused by DIC.