H+ coupled transport of orally active cephalosporins lacking an alpha-amino group across brush-border membrane vesicles from rat small intestine.

The effect of an inwardly directed H+ gradient' on the transport characteristics of ceftibuten, cefixime and analogues of ceftibuten in rat intestinal brush-border membrane vesicles have been investigated. In the presence of a transmembrane H+ gradient, ceftibuten and its analogues exhibited a peak to equilibrium overshoot and an accumulation in the vesicles against the concentration gradient. However, the uptake of cefixime and S-1006 [(6R, 7R)-(7-[(Z)-2-(2-aminothiazol-4-yl)-2-pentenoylamino]-8-oxo- 3- carbamoyloxy-methyl-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxyl ic acid), which lacks a carboxyl group at position 4 of carboxyethylidene structure, exhibited no overshoot, although the equilibrium uptake was increased by a H+ gradient. The equilibrium uptake was dependent on the pH of the final incubation medium and the H+ gradient. These data suggested that the orally active cephalosporins were transported into rat intestinal brush-border membrane by the transmembrane H+ gradient and the pH of the medium.