Acceleration of cholesterol phase transitions in analog bile by chlorpromazine, pentobarbital and ethinyl estradiol

The effects of incorporation of chlorpromazine, pentobarbital and ethinyl estradiol on the maintenance of cholesterol supersaturation was studied in bile analogs. Bile solutions were initially supersaturated and microscopically clear. Chlorpromazine and pentobarbital were almost totally solubilized; ethinyl estradiol was poorly solubilized. Chlorpromazine and pentobarbital in concentrations of 5 and 10 mg/ml rapidly (less than 3-5 h) diminished cholesterol in bile filtrates compared to controls; ethinyl estradiol did so at a concentration of 1 mg/ml but less rapidly (24 h). Bile acid and lecithin concentrations, over time, did not differ significantly between groups. The results indicate that drug interactions with bile constituents, without causing their precipitation, can alter the maintenance of cholesterol supersaturation and phase transitions in bile.