Transcellular and paracellular contribution to transport processes in the colorectal route

The two permeation pathways for colorectal drug absorption, the transcellular and paracellular pathways, were examined. The transcellular pathway is generally a principal route for drugs with some degree of lipophilicity. The contribution of the paracellular pathway to drug absorption is significant when absorption enhancers such as capric acid (C10) and decanoylcarnitine (DC) are used. The action mechanism of C10 on the transcellular pathway was examined by membrane perturbation. The following in vitro effects of C10 on the paracellular pathway were observed: (i) an increase in the equivalent pore radius; (ii) an increase in the permeabilities of water-soluble non-electrolytes and ionic drugs; (iii) a decrease in the junctional resistance and an increase in the membrane capacitance. The action mechanism of C10 in the paracellular pathway was especially elucidated by stimulation to the contraction of the perijunctional actomyosin ring. Finally, an in vivo C10 effect was also observed, as an enhancement of rectal drug absorption from suppositories in rats. (C) 1997 Elsevier Science B.V.