A new model to assess deoxycholic acid metabolism in health using stable isotope dilution technique

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Abstract
A model has been developed that permits calculation of the absorption rates of newly formed and deconjugated deoxycholic acid (DCA) from the intestine, the fractional absorption rate of deconjugated DCA and the daily rate of formation of DCA. The model is based on steady state conditions and isotopic equalities of conjugated DCA in blood and in the enterohepatic circulation, as well as between unconjugated DCA in blood and in the intestinal content. The model requires measurement of isotopic enrichment in the conjugated and unconjugated fractions of DCA in serum after administration of an isotopic label. The measurements were carried out in seven healthy volunteers using capillary gas chromatography/mass spectrometry after oral administration of 24-13C-DNA. Intestinal absorption of deconjugated DCA exceeded that of newly formed DCA: (mean .+-. SD) 7.4 .+-. 5.6 vs. 4.5 .+-. 2.1 .mu.mol kg-1 d-1. Total absorption of unconjugated DCA (11.9 .+-. 6.9 .mu.mol kg-1 d-1) accounted for approximately 6% of estimated total intestinal DCA absorption. The fractional absorption rate of unconjugated DCA in the intestine averaged 55.5 .+-. 15.1%; 8.2 .+-. 3.3 .mu.mol kg-1 d-1 DCA were formed daily by 7.alpha.-dehydroxylation of cholic acid. This rate of DCA formation compares well with values for foecal DCA excretion (15 .mu.mol kg-1 d-1) and cholic acid synthesis rate (11.9 .mu.mol kg-1 d-1) obtained in comparable controls by the same laboratory. Also good agreemment is obtained with data calculated for 7.alpha.-dehydroxylation of cholic acid in the fasting state by Hofmann et al. (J. Clin. Invest. 1983; 71:1003-22) using a simulated physiological pharmacokinetic computer model (5 .mu.mol kg-1 d-1).