DIFFERENTIATED INTESTINAL EPITHELIAL-CELL LINES AS IN-VITRO MODELS FOR PREDICTING THE INTESTINAL-ABSORPTION OF DRUGS

The oral absorption of a compound is a critical factor for the future of the compound as a drug. This absorption is mainly controlled by the passage across the intestinal epithelium. Thus, the prediction of the intestinal absorption by means of an in vitro model may represent a powerful tool for the early selection of molecules during the process of drug development. In the present study, the differentiated human intestinal epithelial cell line HT29-18-C-1, was grown on permeable filters in dual chambers. These cells formed tight monolayers that were used to measure in vitro the transepithelial permeability coefficient (P-c) of various molecules. The results were compared with in vivo data of oral absorption. A threshold value of in vitro permeability of 2 x 10(-6) cm/s was found. Molecules having a permeability coefficient higher than this value were absorbed orally more than 80%, while drugs with P-c values lower than 2 x 10(-6) cm/s were poorly absorbed. By mathematical simulation, it was found that this P-c value, when extrapolated to the surface area and volume of the small intestine, corresponds to an absorption of 80% for a compound with a transit time through the small intestine of 5 h. This demonstrates the predictive utility of the threshold value of the permeability coefficient derived from the in vitro model of intestinal epithelium.