Use of a Caco-2 cell culture model for the characterization of intestinal absorption of antibiotics

The use of cell culture models, based on human cell lines derived from the intestinal epithelium, is a promising new tool for the in vitro study of oral absorption of drugs. An assay has been developed using the Caco-2 cell line with the aim of studying the in vitro permeability of antibiotics. The reproducibility of the assay conditions have been assessed by means of the transport of two different marker molecules: H-3-mannitol and fluorescein, and transepithelial electrical resistance (TEER) value for cells monolayers. The results show that cells after 21 days of culture give significantly tighter monolayers than those after 15 days with higher reproducibility. Apparent permeability coefficients (Papp) have been measured for 13 antibiotics, known to be absorbed at different rates in humans. Papp values span from 0.18 x 10(-6) cm/s for cephaloridine to 5.79 x 10(-6) cm/s for rifampicin where the corresponding bioavailability values, known from literature, span from <3 to 98%. A Caco-2 in vitro model appears to be suitable to investigate the transport of drugs across the intestinal epithelium. This model gives no information about the metabolic phase that follows the absorption of a drug but could provide information to investigate its pharmacokinetical behavior. (C) 1999 Elsevier Science S.A. All rights reserved.