Rate-limiting barriers to intestinal drug absorption: a review

The intestinal epithelium is composed of several structures that could serve as barriers to the transfer of drugs from the GI lumen to the systemic circulation. An aqueous stagnant layer that overlies the apical membrane and the subepithelial blood flow are potential barriers to the absorption of drugs that readily penetrate the absorbing cell of the epithelium. The apical, basal, and basement membranes are potential barriers to the absorption of less permeable drugs. The cytoplasm of the absorbing cell is a relatively, thick barrier that must also be traversed. While the location and structure of these potential barriers are well known, those barriers that are operative and the kinds of molecules for which they are operative are not known. The structure and permeability properties of the potential barriers are considered, along with the roles of the paracellular pathway and countercurrent exchange in the villus circulation.