TY - JOUR
T1 - Ntestinal absorption mechanism of amino-β-lactam antibiotics. III. Kinetics of carrier-mediated transport across the rat small intestine in situ
AU - Nakashima, Emi
AU - Kagatani, Seiya
AU - Tsuji, Akira
AU - Yamana, Tsukinaka
PY - 1984
Y1 - 1984
N2 - The transport kinetics of amino-β-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 cephra-dine. 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-β-lactam antibiotics is closely related with that of dipeptides.
AB - The transport kinetics of amino-β-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 cephra-dine. 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-β-lactam antibiotics is closely related with that of dipeptides.
KW - absorption mechanism
KW - amino-β-lactam antibiotics
KW - carrier-mediated transport
KW - competitive inhibition
KW - critical micelle concentration
KW - dipeptide
KW - in situ recirculating perfusion
KW - intestinal absorption in rat
KW - rat pharmacokinetics
KW - transport process
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U2 - 10.1248/bpb1978.7.452
DO - 10.1248/bpb1978.7.452
M3 - Article
C2 - 6491864
AN - SCOPUS:0021149894
VL - 7
SP - 452
EP - 464
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
SN - 0918-6158
IS - 7
ER -