SELECTIVE PARACELLULAR PERMEABILITY IN 2 MODELS OF INTESTINAL-ABSORPTION - CULTURED MONOLAYERS OF HUMAN INTESTINAL EPITHELIAL-CELLS AND RATINTESTINAL SEGMENTS

New data on the permeabilities of hydrophilic markers in two commonly used in vitro models, i.e., excised intestinal segments from the mt an d monolayers of Caco-2 cells, are presented. The results are compared to human in vivo data. Two groups of hydrophilic marker molecules were tested: (1) monodisperse polyethylene glycols of molecular weights ra nging from 194 to 502 g/mol and (2) a heterogeneous group of molecules consisting of urea, creatinine, erythritol, and mannitol (60-182 g/mo l). The permeabilities of the marker molecules showed a nonlinear depe ndence on the molecular weight and decreased in the order rat ileum > rat colon > Caco-2 cells. Surprisingly, the polyethylene glycols perme ated more easily than the other marker molecules, indicating that char acteristics other than molecular weight, e.g., the flexibility of the structure, may also be important for permeation through the membrane. Comparisons with the published permeability profiles of polyethylene g lycols in human intestinal segments in vivo (i.e., calculated permeabi lity coefficients as a function of molecular weight) indicate that the human intestine is more permeable than the in vitro models. However, the permeability profiles of the corresponding segments in the human i ntestine and the in vitro models were comparable. Thus, good correlati ons were established between permeabilities of the human ileum and rat ileum and between those of human colon, rat colon, and the Caco-2 cel ls. We conclude that the paracellular absorption in humans can be stud ied mechanistically in these in vitro models.