DIFFERENCES IN THE ENHANCING EFFECTS OF SODIUM CAPRATE ON COLONIC AND JEJUNAL DRUG ABSORPTION

We examined the enhancing effect of sodium caprate (C-10) on the jejunal absorption of a poorly absorbed drug, cefmetazole, in rats, in comparison with its colonic absorption (Pharm. Res. 5, 341-346, 1988). Jejunal absorption was significantly enhanced by C-10, but to a smaller extent than colonic absorption. Membrane perturbation. caused by the interaction between C-10 and membrane proteins or lipids, was shown to increase transcellular drug permeability, as reported in the colon. Paracellular permeabilities, obtained from the permeabilities of water-soluble nonelectrolytes of various molecular weights, showed a two-phase pattern against their free diffusion coefficients, suggesting the existence of at least two pore routes similar to those in the colon. C-10 increased paracellular permeability in the colon but not in the jejunum. Impedance analysis and voltage clamp technique in the jejunum showed no significant effect of C-10 on paracellular permeability, such as found in the colon. Accordingly, the difference in the effects of C 10 on the jejunal and colonic absorption of cefmetazole was due mainly to the difference in its effects on the paracellular pathway.