Theoretical Model Studies of Intestinal Drug Absorption IV: Bile Acid Transport at Premicellar Concentrations across Diffusion Layer-Membrane Barrier

A general physical model is described for the simultaneous active and passive transport of conjugated and unconjugated bile acids from nonmicellar solutions in the ileum. It reduces to the passive absorption mechanism in the duodenum and jejunum. The model provides the basis for the experimental design of in situ studies and the quantification of physically meaningful and experimentally accessible transport parameters and of the effect of functional groups on bile acids. The interaction and factorization of (a) the permeability of the stagnant water layer, the lipoidal and aqueous channel pathway of the membrane according to the diffusion mechanisms, (b) the permeability of the membrane according to the active mechanism, (c) the bile acid concentration dependence, and (d) the pH and pKa are mathematically explicit. Theoretical computations indicated that the stagnant water layer may be the rate-determining barrier. A model is described for the first-pass absorption of bile acids from dilute solutions in the small intestine.