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The transport kinetics of amino-beta-lactam antibiotics was studied by an in situ rat small intestinal recirculating perfusion technique. The disappearance rates of the antibiotics from the perfusing luminal solution followed mixed-type kinetics with saturable and nonsaturable processes. The kinetic parameters were determined. Pharmacokinetic analysis of the time courses of luminal disappearance, tissue accumulation, and blood concentration indicated that the transfer of the antibiotics from the in situ luminal solution to tissue is nearly irreversible. On the assumption that the saturable transport process involves a common carrier for these antibiotics, the predicted extents of mutual inhibition using the in situ kinetic parameters were in good agreement with the experimental values for cephalexin and cephradine. The effects of cephalexin and cefadroxil on the absorption of cyclacillin were also consistent with a common transport mechanism. The dipeptides, carnosine and L-phenylalanylglycine markedly inhibited cyclacillin absorption in a competitive fashion. Furthermore, cyclacillin inhibited the absorption of carnosine. The results indicate that the absorption of amino-beta-lactam antibiotics is closely related with that of dipeptides.

journal of pharmacobio-dynamics

Intestinal absorption mechanism of amino-.BETA.-lactam antibiotics. III. Kinetics of carrier-mediated transport across the rat small intestine in situ.