Enhancement of colonic drug absorption by the paracellular permeation route

Abstract

Colonic absorption of poorly absorbable cefmetazole was shown to increase considerably by the addition of 1% sodium caprate, sodium laurate, and mixed micelles composed of sodium oleate and sodium taurocholate. At 0.25%, their effects were weaker but still significant. Colonic absorption of inulin was also increased by the promoters at a concentration of 0.25%. These results suggest that there is a common route between inulin and cefmetazole absorption, i.e., the paracellular route. Sodium taurocholate, sodium caprylate, and EDTA disodium salts (EDTA-2Na) at 1% enhanced cefmetazole absorption less than caprate, laurate, or mixed micelles, but no such effect was found at 0.25%. The colonic pore radius was determined from the equivalent pore theory using an everted sac procedure. Caprate, laurate, and mixed micelles at 0.25% caused this radius to increase significantly, thus making it possible for inulin to permeate the everted sac from the mucosal to the serosal side. The effects of taurocholate, caprylate, and EDTA-2Na for increasing colonic pore sizes and the degree of inulin permeation were less than those of caprate, laurate, or mixed micelles. The change in the paracellular route is thus considered to result from the increase in pore size.