Choleresis and hepatic transport mechanisms

Summary To investigate binding of drugs to biliary micelles as a possible factor in the hepatic transport process, interaction of two uncharged compounds, ³H-ouabain and ³H-K-strophanthoside with biliary micelles was studied by ultracentrifugation of bile. The various bile acids normally present in rat bile were predominantly associated with cholesterol containing micelles, but not to the same extent. The tendency of the bile salts to be associated with mixed micelles was the greatest for conjugated chenodeoxycholate, somewhat lower for conjugated deoxycholate and the least for conjugated cholate. The sedimentation patterns of the water-soluble cardiac glycosides, added in vitro, indicated binding to mixed biliary micelles as well as non-cholesterol containing micelles. Also mannitol, a drug used to estimate canalicular bile flow, was found to be associated with both categories of biliary micelles.In spite of the binding of cardiac glycosides to the micelles, administration of taurocholate, which promotes formation of biliary micelles, did not stimulate biliary output of both glycosides. Also administration of the choleretics dehydrocholate and ethacrynic acid failed to enhance biliary output of the glycosides.These results indicate, that binding of drugs to biliary micelles diminishes the free concentration of drugs in bile and confirms earlier studies with organic anions that binding to biliary micelles is not a pertinent factor in the rate of biliary excretion.