The uptake of orally active cephalosporins, ceftibuten and cephradine, by intestinal brush-border membrane vesicles isolated from man, rat and rabbit was studied. In the presence of an inward H+ gradient, ceftibuten but not cephradine was taken up into intestinal brush-border membrane vesicles of man and rat against the concentration gradient (overshoot phenomenon). In rabbit jejunal brush-border membrane vesicles, the uptake of both cephalosporins in the presence of an inward H+ gradient exhibited the overshoot phenomenon. In human and rat vesicles, the initial uptake of ceftibuten was strongly inhibited by compound V, an analogue of ceftibuten, but the uptake of cephradine was not affected by any of the cephalosporins tested, whereas in the rabbit brush-border membrane vesicles, initial uptake of both ceftibuten and cephradine were markedly inhibited by all cephalosporins and dipeptides used. These results suggest that the transport characteristics of human and rat intestinal brush-border membrane for cephalosporins are comparable, and that rabbit is an inadequate animal for investigating the transport characteristics of beta-lactam antibiotics.
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