HT29-MTX CACO-2 COCULTURES AS AN IN-VITRO MODEL FOR THE INTESTINAL EPITHELIUM - IN-VITRO IN-VIVO CORRELATION WITH PERMEABILITY DATA FROM RATS AND HUMANS/

The diverse secretory and absorptive functions of the intestinal epith elium are conducted by a mixed population of absorptive cells and mucu s-producing goblet cells as the major cell types. In order to approach the main characteristics in an in vitro model, a coculture system of absorptive Caco-2 cells and mucus-secreting HT29-MTX cells was develop ed and the permeability of a range of different drugs was tested. Vari able goblet cell frequency can be achieved, preserving a significant b arrier to drug transport and maintaining the differentiated features o f both cell types. Absorption rates for actively transported drugs are rather underestimated in the cell culture model when compared to in v ivo data. However, a good correlation with fraction absorbed in humans was attained separating the range of passively transported drugs into two groups of well-absorbable compounds with P-eff greater than or eq ual to 10 x 10(-6) cm/s and drugs that are absorbed 40-70% with P-eff = 0.1-1 x 10(-6) cm/s. A permeability of P-eff < 0.1 x 10(-6) cm/s is suggested for low absorbable drugs.