Determination of cholic acid and chenodeoxycholic acid pool sizes and fractional turnover rates by means of stable isotope dilution technique, making use of deuterated cholic acid and chenodeoxycholic acid.
A procedure is described for the simultaneous determination of cholic acid and chenodeoxycholic acid pool sizes and fractional turnover rates. After oral administration of known amounts of 11,12-dideuterated chenodeoxycholic acid and 2,2,4,4-tetradeuterated cholic acid, the ratios of chenodeoxycholic acid-D2/chenodeoxycholic acid and cholic acid-D4/cholic acid are measured in consecutive serum samples, after which fractional turnover rates and pool sizes of chenodeoxycholic acid and cholic acid are determined arithmetically. In 7 healthy volunteers pool sizes for chenodeoxycholic acid and cholic acid were 22.9 +/- 7.8 and 24.1 +/- 11.7 mumol/kg, respectively. The corresponding values for the fractional turnover rates were 0.23 +/- 0.10 and 0.29 +/- 0.12/day. After oral administration of the labelled bile acids in capsule, the obtained pool sizes were significantly higher than after administration in a bicarbonate solution. Bile acid kinetics were also performed in a patient suffering from a cholesterol synthesis deficiency and in a patient very likely suffering from a bile acid synthesis deficiency. Furthermore, the kinetics of the intestinal absorption and hepatic clearance of unconjugated bile acids have been investigated in 2 healthy subjects.
D000328:Adult; D001639:Bicarbonates / Q000008:administration & dosage; D002214:Capsules; D002635:Chenodeoxycholic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D019826:Cholic Acid; D002793:Cholic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003903:Deuterium; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007201:Indicator Dilution Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D012996:Solutions
D001639:Bicarbonates; D002214:Capsules; D002793:Cholic Acids; D012996:Solutions; D002635:Chenodeoxycholic Acid; D003903:Deuterium; D019826:Cholic Acid