The effects of FUT-175 (nafamostat mesilate) on blood coagulation and experimental disseminated intravascular coagulation(DIC).

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Abstract
FUT-175 is a newly synthesized serine protease inhibitor. In the present study, we investigated the effects of FUT-175 on blood coagulation and experimental DIC. The effects on coagulation were examined in vitro by measuring the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) of rat plasma in the presence of FUT-175. FUT-175 exhibited remarkable anticoagulative effects to prolong APTT at a plasma concentration of 3 .times. 10-7M, PT at 1 .times. 10-5 M and TT at 3 .times. 10-5 M. The anticoagulative effect of FUT-175 at 1 .times. 10-6 M on APTT was almost similar to that of heparin at 0.3 U/ml or that of gabexate mesilate at 1 .times.10-3 M. Experimental DIC was induced by a four-hr sustained intravenous infusion of endotoxin. FUT-175 was administered intraperitoneally prior to the injection of endotoxin or infused intravenously with endotoxin. As a result, the prolongation of APTT and PT, the decreases of fibrinogen level, platelet counts and complement level, and the increase of FDP were remarkably improved by FUT-175. Furthermore, glomerular fibrin deposits were reduced by the infusion of FUT-175. These results indicate that FUT-175, having a potent inhibitory effect on blood coagulation, is clinically applicable to therapy for DIC.

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