Speed of change in biliary lipids and bile acids with chenodeoxycholic acid--is intermittent therapy feasible?
To see whehter intermittent chenodeoxycholic acid (CDCA) therapy is a potential alternative to continous treatment for gallstone dissolution, the speed of change in bile lipid composition was studied after starting and stopping CDCA therapy. In addition, the relationship between bile lipid composition and the proportions of the bile acids was examined. Bile-rich duodenal fluid was collected twice in the first week and then at approximately weekly intervals for four to six weeks, from six gallstone patients starting 13-15 mg CDCA.kg BW-1 day-1 and from another group of six patients whose treatment was stopped after gallstone dissolution. After starting treatment, the mean biliary cholesterol saturation index (based on criteria of Hegardt and Dam, 1971) decreased from 1-49 +/- SEM 0-17 to 0-92 +/- 0-13 at three weeks and 0-88 +/- 0-10 at four weeks, by which time bile lipid composition had become relatively constant. In patients whose treatment was stopped, bile reverted to its supersaturated state within one week, changing from an on-treatment mean saturation index of 0-74 +/- 0-10 to 1-15 +/- 0-15 in six to eight days after withdrawing CDCA. The proportion of conjugated CDCA in the biliary bile acids increased from 27-9 +/- 2-5% to 60-5 +/- 4-2% within four days and to 80-7 +/- 6-2% by four weeks after starting CDCA. When treatment was stopped, the proportion of CDCA reverted to pretreatment levels by two to three weeks. The saturation index was significantly related (P less than 0-001) to the percent of conjugated CDCA present, such that when the proportion of CDCA exceeded 70%, bile was almost invariably unsaturated. Since the mean time taken for bile to become unsaturated was not shorter than the time taken for bile to revert to its supersaturated state, it seems that intermittent treatment would not be adequate to maintain an unsaturated bile and is, therefore, unlikely to be as effective as continuous treatment in dissolving gallstones.
D000328:Adult; D000368:Aged; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D002769:Cholelithiasis / Q000188:drug therapy* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged
D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D002784:Cholesterol