Comparison between active and passive drug transport in human intestinal epithelial (Caco-2) cells in vitro and human jejunum in vivo

Drug transport rates in Caco-2 monolayers were compared with those obtained in the human jejunum in vivo. Permeability coefficients unbiased by the hydrodynamic conditions were calculated in order to allow direct comparison of the two models. The rapidly (passively) transported drugs naproxen, antipyrine and metoprolol had comparable permeability coefficients in Caco-2 cells and in human jejunum. The permeability coefficients of the slowly (passively) transported, hydrophilic drugs, terbutaline and atenolol, 79- and 27-fold lower, respectively, in Caco-2 cells than in jejunum. The carrier-mediated transport rates of L-dopa, L-leucine and D-glucose were also much slower in Caco-2 cells than in human jejunum. The lower permeability of the actively transported compounds and of atenolol and terbutaline is consistent with the colonic origin of the Caco-2 cells. The results indicate that Caco-2 monolayers can be used to predict passive drug transport in humans, while prediction of transport by carrier-mediated systems may require a scaling factor, due to a low expression of carriers in this cell line.