Simulation of the metabolism and enterohepatic circulation of endogenous deoxycholic acid in humans using a physiologic pharmacokinetic model for bile acid metabolism

The metabolism and enterohepatic circulation of deoxycholic acid (DCA), a major secondary bile acid in humans, was simulated using a linear multicompartmental physiologic pharmacokinetic model. The model was similar to that previously reported and used to simulate the metabolism of cholic acid and chenodeoxycholic acid, but differed in two respects: (a) the input of newly formed DCA molecules originated from colonic absorption rather than from de novo hepatic biosynthesis and (b) a new type of transfer coefficient was proposed to describe the movement of DCA molecules from an insoluble, bound compartment to a soluble compartment. Simulations were performed to define the effect of varying fractional colonic absorption (from 0.1 to 0.6) as well as varying fractional formation of DCA from cholic acid (from 0.3 to 1). The simulations indicated that the exchangeable total DCA pool expanded up to 12-fold as fractional colonic absorption was increased from 0.1 to 0.6. The fractional turnover rate of the DCA pool showed a corresponding decrease. Increased conversion of cholic acid to DCA had an effect on DCA pool size that was similar to that resulting from increased colonic fractional absorption. So long as ileal absorption was efficient, the “soluble” colonic pool of DCA remained small relative to other organ pools, and the absorption of unconjugated DCA from the colon was