Continuous regional application of protease inhibitor in the treatment of acute pancreatitis. An experimental study using closed duodenal obstruction model in dogs.

In clinical settings, the effectiveness of protease inhibitors in the treatment of acute pancreatitis has been still controversial. With the concept that sufficient tissue concentration of protease inhibitor in the pancreas has to be included to achieve its potent inhibitory effect, we applied a continuous regional intra-arterial (CRI) application of low-molecular-weight protease inhibitor, nafamostat mesilate (FUT-175), for closed duodenal loop obstruction model in mongrel dogs. The use of CRI application led to a higher concentration of FUT-175 in the pancreatic tissue (4,453 +/- 758 ng/g) when compared with that applied intravenously (905 +/- 48 ng/g). Consequently, pancreatic parenchyma in CRI application animals was remarkably preserved, as assessed by the lower extent of pancreatic necrosis (12.4 +/- 2.6% in CRI vs. 25.6 +/- 1.9% in intravenous). Additionally, the elevation of trypsin-like activity in the pancreas was significantly inhibited in CRI animals. Based on these findings, the dose as well as the route of protease inhibitors should be carefully considered to achieve its beneficial effect.