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

Clin Chim Acta. 1988 Jul 15;175(2):143-55. doi: 10.1016/0009-8981(88)90004-6.

Abstract

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.

MeSH terms

  • Adult
  • Bicarbonates / administration & dosage
  • Capsules
  • Chenodeoxycholic Acid / administration & dosage
  • Chenodeoxycholic Acid / pharmacokinetics*
  • Child
  • Cholic Acid
  • Cholic Acids / administration & dosage
  • Cholic Acids / pharmacokinetics*
  • Deuterium
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Indicator Dilution Techniques
  • Intestinal Absorption / drug effects
  • Male
  • Solutions

Substances

  • Bicarbonates
  • Capsules
  • Cholic Acids
  • Solutions
  • Chenodeoxycholic Acid
  • Deuterium
  • Cholic Acid