Inhibitory effects of gabexate mesilate (FOY) on experimental DIC

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Abstract
In Japan, gabexate mesilate (FOY) has been synthesized as a newly therapeutic agents for pancreatitis. It has been known that this protease inhibitor affects trypsin, plasmin, plasma kallikrein, thrombin and Cl-esterase. In this paper, the inhibitory effects of FOY on experimental DIC were investigated in comparison with those of aprotinin or heparin. 32 rabbits (matured male, body weight from 2.5 to 3.0kg) were used as experimental animals. These were divided into three groups. Each group was pretreated by infusion of FOY, aprotinin or heparin with 20mg/kg, 10, 000KIE/kg or 400 Units/kg respectively, and immediately after the infusion, thrombin, tissue thromboplastin or endotoxin were infused as DIC inducers. Several parameters (platelet counts, white blood cells, neutrophils, fibrinogen, FDP, platelet retention, platelet aggregation (ADP-induced), prothrombin time and partial thromboplastin time) were investigated before and after infusions of trigger substances. The changes of these parameters were expressed in accordance with the score system which had been ready beforehand, and then the inhibitory effects of these drugs on experimental DIC were examined statistically. The results obtained are as follows; 1) Total scores of each group in thrombin-induced DIC were 31, 10, 24 and 21, in groups of control, FOY, aprotinin and heparin respectively. Scores in drug-pretreated group were significantly smaller than those in control group (P<0.05). In particular, the score of FOY was lower than those of the other groups statistically (p<0.05). 2) In tissue thromboplastin-induced DIC, scores were 35, 26, 24 and 20 in control, FOY, aprotinin and heparin each other, with no significant differences among the drug groups. 3) Scores in endotoxin-induced DIC were 39, 28, 29 and 31 in groups of control, FOY, aprotinin and heparin, respectively, showing no significant differences. In conclusion, the results of the present study suggest that FOY was more effective than heparin or aprotinin on the inhibition of experimental DIC.

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