ESTIMATION OF ORAL-DRUG ABSORPTION IN MAN BASED ON INTESTINE PERMEABILITY IN RATS

Predicting the fraction of an oral dose absorbed in humans is of consi derable interest at an early stage of a research program in the pharma ceutical industry. Models described in the literature to predict the o ral absorption in man include: the permeability in Caco-2 cells, absor ption from a perfused segment of rat intestinal lumen and uptake into everted rings. The present study used an isolated and vascularly perfu sed rat small intestine to determine the permeability values of eleven compounds across the intestinal epithelium. A good correlation was ob tained between the permeability values determined in this model and th e proportion of an oral dose absorbed in humans. Compared to the other models, the present one could allow the appearance in the artificial bloodstream and the intestinal metabolism of a compound to be studied simultaneously.