Effect of a new synthetic trypsin inhibitor on taurocholate-induced acute pancreatitis in rats.
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.
Sobajima
H
H
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Hayakawa
T
T
Kondo
T
T
Shibata
T
T
Kitagawa
M
M
Sakai
Y
Y
Ishiguro
H
H
Tanikawa
M
M
Nakae
Y
Y
D000208:Acute Disease; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D013656:Taurocholic Acid; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D006146:Guanidines; D014361:Trypsin Inhibitors; D013656:Taurocholic Acid; C062836:ONO 3307