Abstract
The effects of the absorption promoters on two possible pathways, paracellular and transcellular routes, were investigated physiologically or biochemically. Assuming the paracellular route to be a water channel since the permeation through this route related to water absorption, the pore size was obtained from the equivalent pore concept using intestinal everted sac. Sodium caprate, sodium laurate, mixed micelles composed of sodium oleate and sodium taurocholate, EDTA disodium salts, which had larger promoting effects on the intestinal absorption of cefmetazole, fosfomycin and phenol red than other promoters, enlarged the pore size to the extent that inulin could permeate. For the transcellular route, the membrane perturbing actions of the promoters were examined using brush border membrane vesicles, where its protein and lipid portions were labelled with fluorescent probes, and a fluorescence polarization technique. The interaction of the potent promoter such as sodium caprate and membrane protein or lipids was found to cause membrane perturbation and increase the membrane permeability. In this minireview, one methodology for the mechanistic study on drug absorption promotion was introduced as described above. Consequently, the changes in the paracellular and transcellular routes could be found specifically, to explain the in situ absorption promotion of poorly absorbed drugs quantitatively.
