Dissolution kinetics of cholesterol in simulated bile II: influence of simulated bile composition.

Normal human gallbladder bile and gallbladder bile of patients undergoing chenodeoxycholic acid therapy were simulated by using appropriate combinations of taurine and glycine conjugates of cholic, chenodeoxycholic, and deoxycholic acids. Also, the total bile acid concentration and the total bile acid to lecithin ratio were varied over physiological ranges. Dissolution rates of cholesterol monohydrate pellets (model gallstone) in these solutions were 90--99% interfacially controlled. Even under conditions favorable for dissolution, i.e., high bile acid concentration and high bile acid to lecithin ratio, the interfacial resistances were extremely large. These results are of the same order of magnitude as those found in the limited studies with actual gallbladder bile and suggest that the bile acids, lecithin, and the electrolytes are the primary determinants of the interfacial resistance for cholesterol dissolution. Furthermore, the kinetics of dissolution were always much faster with the chenodeoxycholic acid-rich compositions than with the corresponding normal compositions. This finding suggests, therefore, that in addition to desaturating bile with respect to cholesterol, the feeding of chenodeoxycholic acid further facilitates cholesterol gallstone dissolution by reducing the interfacial resistance of the process.