Effect of a new synthetic trypsin inhibitor on taurocholate-induced acute pancreatitis in rats.

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.

• Authors: H Sobajima, T Hayakawa, T Kondo, T Shibata, M Kitagawa, Y Sakai, H Ishiguro, M Tanikawa, Y Nakae
• Journal: Pancreas (Pancreas) Vol. 8 Issue 2 Pg. 240-7 (Mar 1993) ISSN: 0885-3177 [Print] United States
• PMID: 8460097 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Guanidines
• Trypsin Inhibitors
• Taurocholic Acid
• ONO 3307

Topics

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