Camostate (FOY-305) improves the therapeutic effect of peritoneal lavage on taurocholate induced pancreatitis

Abstract

The effect of peritoneal lavage with the addition of camostate to the lavage fluid on the outcome of taurocholate pancreatitis in rats was studied. Camostate is a low molecular weight protease inhibitor which has been developed recently. Peritoneal lavage was performed for 12 hours and camostate was added to the lavage fluid in five concentrations. At 0.1 mg/ml the survival rate increased significantly (11 of 20 v controls 4 of 20, p less than 0.05); the maximal effect was observed at 0.2 mg/ml, and no effect was seen at 0.01 and 0.05 mg/ml. Adverse effects occurred at 0.5 mg/ml. The addition of 0.1 mg/ml camostate significantly reduced the acidosis in arterial blood: mean (SD) pH 7.30 (0.035) v controls 7.23 (0.054) (n = 9, p less than 0.01) and arterial base excess: -15.4 (1.26) mmol/l v controls: -17.4 (2.51) mmol/l (n = 9, p less than 0.05). There was no difference, however, in plasma amylase activity and in the histological degree of specific tissue damage to the pancreas. A combination of intravenous camostate and lavage with the addition of camostate to the lavage fluid yielded a significantly improved survival compared with treatment with intravenous camostate alone (10 out of 16 animals v intravenous camostate alone, two out of 16, p greater than 0.01). We conclude that lavage with camostate significantly improves the prognosis of severe necrotising pancreatitis in rats.