Effect of Camostat Mesylate on Chemical Compositions of Bile and Crystallization in Gallbladder Stone Patients

ABSTRACT

BACKGROUND: It has been well demonstrated that trypsin inhibitor can stimulate the secretion of cholecystokinin. Camostat mesylate (C20H22N4O5 CH3SO3H) is a synthetic trypsin inhibitor. We demonstrated the effect of camostat mesylate on the chemical composition of bile and the crystallization in gallbladder-stone patients. METHODS: Gallbladder bile sample from 22 patients with GB stones were analyzed. In 11 patients, camostat mesylate (Foy-pan ) was administered orally in a dosage of 600 mg per day for more than 5 days, and the results of the bile analysis were compared to those of 11 controls. RESULTS: The total protein concentration in the camostat group was lower than that in control group (0.21+/-0.10 vs 0.24+/-0.06 g/dl) but the difference was not significant (p=0.41). The total bile acid concentration in the camostat group was significantly lower than that in the control group (5.47+/-1.56 vs 6.85+/-1.32 g/dl, p=0.04). The concentrations of cholesterol and phospholipid were lower in the camostat group (0.35 +/- 0.19 vs 0.44 +/- 0.11 g/dl, 2.10 +/- 1.19 vs 2.92 +/- 0.93, respectively), but the differences were not statistically significant (p=0.20, p=0.09, respectively). The total lipid concentration which reflects the concentrated magnitude of the bile, was significantly lower in the camostat group (7.93 +/- 2.87 vs 10.20 +/- 2.01 g/dl, p=0.04). The cholesterol saturation index didn't demonstrate a significant difference between the two groups (1.06 +/- 0.27 vs 0.95 +/- 0.31, p=0.38). Crystallization in the bile from cholesterol stone patients, was observed every day for 7 days. Crystallizations was less frequent in the camostat group, but the difference was not statistically significant (1/6 vs 4/8, p=0.39). DISIDA (disofenin iminediacetate) scans were performed in 3 healthy volunteers to observe the changes in the radioactivities and the volumes of the gallbladders before and after the administrations of camostat. The peak radioactivities, the transittime to the peak radioactivity, and the gallbladder volume at the peak radioactivity in the scan after the administration of camostat were lower than in the corresponding values before the administration. CONCLUSIONS: Camostat mesylate lowers the concentration of all bile components. We assume that the effects of Camostat mesylate are mediated by CCK, which enhances gallbladder motility and limits the concentrating function of the gallbladder.