Effect of a New Synthetic Trypsin Inhibitor on Taurocholate-Induced Acute Pancreatitis in Rats

Pancreas. 1993 Mar;8(2):240-7. doi: 10.1097/00006676-199303000-00016.

Abstract

The effect of a novel synthetic trypsin inhibitor, 4-sulfamoylphenyl 4-guanidinobenzoate methanesulfonate (ONO-3307), on severe acute pancreatitis was studied by changing its timing, frequency, and dose in trypsin-taurocholate-induced acute experimental pancreatitis in rats. Rats were divided into four groups according to difference of ONO-3307 administration: group A, 2 mg/0.5 ml of ONO-3307 s.c. 1 h before and after induction of pancreatitis; group B, 2 mg/0.5 ml s.c. 1 and 3 h after; group C, 4 mg/1 ml s.c. 1 h before; group D, 4 mg/1 ml s.c. 1 h after. The survival rate at 24 h was significantly improved in group A (75% in A vs. 17% in control; p < 0.01) and in group B (57 vs. 29%; p < 0.05), but not in group C or D. Amylase and immunoreactive trypsin in serum and ascites of the treated were significantly lower than those of controls in both groups A and B. The survival rates were improved dose dependently when ONO-3307 was administered 1 h before and after induction of pancreatitis. ONO-3307 showed favorable effects on the initial stage of severe acute pancreatitis when given in divided doses to maintain the effective serum levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Dose-Response Relationship, Drug
  • Guanidines / pharmacology*
  • Male
  • Pancreatitis / chemically induced
  • Pancreatitis / drug therapy*
  • Rats
  • Rats, Wistar
  • Survival Rate
  • Taurocholic Acid
  • Trypsin Inhibitors / pharmacology*

Substances

  • Guanidines
  • Trypsin Inhibitors
  • Taurocholic Acid
  • ONO 3307