Comparative Assessment of Intestinal Transport of Hydrophilic Drugs Between Small Intestine and Large Intestine

Intestinal passive transport of several hydrophilic drugs (and probe compounds) was examined in the large intestine (colon), in comparison with that in the small intestine, in an effort to obtain basic information for developing rational colonic drug delivery strategies. The drugs tested were polyethylene glycol (PEG 900), L-glucose, D-xylose, 5-fluorouracil (5-FU) and urea. In everted intestinal sacs, the uptake of every drug was larger in the small intestine than in the large intestine, although by various extents. The uptake of urea was larger than those of D-xylose and L-glucose in both the small intestine and large intestine and associated with a larger large intestine (LI)/small intestine (SI) uptake ratio. Assuming that passive transport via the paracellular route (or aqueous pore) is predominant for them, the large intestine may have smaller paracellular (or aqueous) pores, restricting the transport of those monosaccharides compared with smaller molecules such as urea by a larger extent in the large intestine than in the small intestine. The passive transport of 5-FU was significantly larger than those of the monosaccharides in both the small intestine and large intestine and associated with a larger LI/SI uptake ratio, even though 5-FU has a molecular weight close to that of the monosaccharides. 5-FU may be transported predominantly by transcellular diffusion, because its oil-to-water partition coefficient is about 200 times larger than those of the monosaccharides. Although transport mechanisms, including transport pathways, are yet to be fully clarified, drugs with physicochemical properties similar to those of 5-FU or urea may be more feasible for colonic drug delivery than those with physicochemical properties similar to those of monosaccharides.