Comparison of the Intestinal Drug Permeation and Accumulation Between Normal Human Intestinal Tissues and Human Intestinal Tissues With Ulcerative Colitis

Abstract

The purpose of this study was to examine drug absorption profile utilizing human intestinal tissues from ulcerative colitis (UC) patients and to compare with normal tissues from intestinal cancer patients. Human intestinal tissues from UC and cancer patients mounted in a mini-Ussing chamber were used to evaluate the permeation of drugs, including FD-4, a very low permeable marker, rebamipide, a low permeable marker, and metoprolol, a high permeable marker. The transport index, an index of sum of permeated and tissue-accumulated molecules, of the model drugs was in accordance with their absorption rank order, and was almost kept constant irrespective of autopsy grade based on tissue fibrosis. On the other hand, UC tissues of grade 2 showed the decreased Xcorr, an index of permeated amount of molecules and increased Tcorr, an index of tissue-accumulated molecules for every tested compound.Our finding of the transport characteristics in intestinal tissues of severe UC patients in mini-Ussing chamber system demonstrated that autopsy grade of UC patients did not drastically change membrane permeability of the tested compounds. Furthermore, it was suggested that morphological changes of intestinal tissues caused by fibrosis led to limited permeation and subsequently increased accumulation with little change of total absorption.