Mass spectrometry identification of biliary bile acids in bile from patients with gallstones before and during treatment with chenodeoxycholic acid. An ancillary study of the National Cooperative Gallstone Study.
The chemical structure of individual bile acids in 255 duodenal bile samples obtained from patients with radiolucent gallstones before and during treatment with chenodeoxycholic acid (375 or 750 mg/day) was determined by coupled gas chromatography/mass spectrometry. The two primary bile acids, cholic acid and chenodeoxycholic acid, and their metabolic products, deoxycholic acid, lithocholic acid, and ursodeoxycholic acid, were present in all bile samples and constituted greater than 97% of all bile acids. In pretreatment samples, the 12-oxo derivative of deoxycholic acid (3 alpha-hydroxy-12-oxo-cholanoic acid) was the next most abundant bile acid, being present in 62% of the samples; the average concentration was 1%, but three individuals had 6% to 8% of this bile acid. The 7-oxo derivative of chenodeoxycholic acid was also present in the majority of samples, but at a lower proportion (0.3%); five individuals had 2% to 3%. The 7-oxo derivative of cholic acid was present in a minority of samples (37%) in trace concentrations; isodeoxycholic acid and the 3-oxo derivatives of chenodeoxycholic acid and deoxycholic acid were also present in trace amounts. Four patients had 1% to 11% ursocholic acid in bile. During treatment with chenodeoxycholic acid, bile became enriched in it in direct relation to dosage; the concentration of its bacterial metabolites increased, and the proportion of cholic acid and its bacterial metabolites showed a reciprocal decrease. No unusual bile acids appeared, indicating that treatment with these doses of chenodeoxycholic acid does not result in the occurrence of additional uncommon bile acids in bile. It is suggested that the paucity of uncommon bile acids in bile, which contrasts strikingly with the great variety of uncommon bile acids known to be present in urine and feces, is the result of two factors: (1) the conversion of uncommon bile acids to common bile acids by reduction, hydroxylation, or epimerization during hepatic passage; and (2) efficient hepatic transport of common but not uncommon bile acids into bile.
D001646:Bile / Q000032:analysis*; D001647:Bile Acids and Salts / Q000032:analysis*; D002635:Chenodeoxycholic Acid / Q000627:therapeutic use*; D002769:Cholelithiasis / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D001330:Electronic Data Processing; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans
D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid