The transport pathways of the colon allow rapid and specific active bi-directional transport of ions across the epithelial layer. Unlike the small intestine, there are no documented active transporters for organic nutrients in the mature organ and, therefore, no chances for drug molecules to be absorbed in a piggy-back fashion62. The apparent lack of organic nutrient transporters may limit the potential for drug design with respect to carrier mediated transport across the colon, hence drug absorption is a consequence of the general properties and features of the colon. These include transmucosal and membrane potential differences and the bulk water absorption which may allow drug absorption via osmotic solvent drag.
Animal models suggest that sugars such as sucrose and glucose, and amino acids, are poorly absorbed from the adult colon63 64, but the relevance to humans has to be demonstrated, since diet has a major effect on colonic physiology and these studies were carried out in the rat and horse. An in vitro study of the permeability of the rat colonic mucosa suggests that the colon excludes molecules on the basis of size and charge65. It has been calculated that the pore size is 2.3A in the human colon compared to 8A in the jejunum and 4A in the ileum66.
The dissociation of a drug at the absorption site will depend on the pH of the microclimate at the mucosal wall and not the pH of the bulk phase. It is estimated that the unstirred microclimate near the mucosal wall has a thickness or extent of about 840 pm67. The concentration of K+ is lower in the microclimate than the luminal contents, and it is independent of bulk K+ concentration.
The fluidity of the caecal and ascending colon is gradually reduced as the water is reabsorbed. The reduction in the water content means that there is less mixing in the bulk phase and therefore less access to the mucosal surface, along with less water available for drug dissolution. Gas bubbles present in the colon also will reduce contact of drug with the mucosa.
Some viscous soluble dietary fibres may increase the thickness of the unstirred water layer by reducing intraluminal mixing68. Dietary fibres such as pectin and chitosan have cation-exchange properties which may bind drug molecules. These physical factors will all act to slow drug absorption in the colon, with increasing effect as water is removed and the transport properties of the faecal mass are reduced.
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