TRANSPORT OF ORAL CEPHALOSPORINS BY THE H+ DIPEPTIDE COTRANSPORTER AND DISTRIBUTION OF THE TRANSPORT ACTIVITY IN ISOLATED RABBIT INTESTINALEPITHELIAL-CELLS/

Transport of cephalosporins was studied using isolated rabbit intestin al epithelial cells. Cephradine uptake by the cells was concentrative and was inhibited by the addition of glycylsarcosine. The accumulated cephradine was effluxed from the cells by the addition of a protonopho re, carbonyl cyanide 4-tri-fluoromethoxyphenylhydrazone (FCCP). Amilor ide, an inhibitor of the Na+/H+ exchanger, reduced the steady-state up take of cephradine, suggesting that the exchanger contributes to the m aintenance of an inward HC gradient as a driving force. Cephradine upt ake by ATP-depleted intestinal cells was actively driven by the inward H+ gradient and was inhibited by FCCP and glycylsarcosine. The distri bution of cephradine transport activity along the small intestine and villus-crypt axis was also examined in the isolated cells, and the tra nsport activity was higher in the upper parts of the intestinal segmen ts and in villus cells. These results indicate that the uptake of oral cephalosporins by intestinal epithelial cells is concentrative and re versible and that the H+/dipeptide cotransporter and the Na+/H+ exchan ger play an important role for the active uptake of these drugs, The a ctivity of the H+/dipeptide cotransporter should be higher in upper se gments and in villus cells of the small intestine.