Abstract
The effects of intravenous administration of the protease inhibitor, nafamostat mesi-late (FUT-175), on pancreatic exocrine secretion were studied in conscious rats. FUT-175, at two different doses, 0.5 and 1 mg/kg/h, was infused intravenously for four hours in rats. Some 150 ng/ml and 300 ng/ml FUT-175 was excreted into the bile after venous administration of 0.5 and 1 mg/kg/h respectively. Pancreatic flow and protein output were not altered by intra-duodenal infusion of bile-pancreatic juice containing FUT-175. Injection of 300 ng, 600 ng and 0.01 mg/h of FUT-175 into the duodenum for four hours did not significantly increase pancreatic exocrine secretion, or release of CCK. Pancreatic exocrine secretion increased significantly 1.5 hours after intraduodenal administration at 0.1 mg/body/h of FUT-175, whereas plasma CCK levels did not change from basal levels. Although the pancreatic exocrine was dose de-pendently secreted in response to intraduodenal administration of FUT-175, the doses were much higher than the in vivo thereapeutic dose. It was concluded that a therapeutic dose of FUT-175 will not induce pancreatic exocrine secretion in conscious rats.
