Abstract
To elucidate the transport characteristics of the H+/dipeptide carrier that recognizes the orally active β-lactam antibiotic ceftibuten, the uptake behaviors were compared of ceftibuten and Gly-Sar by rat intestinal brush-border membrane vesicles. The results show that 1) both the uptake of ceftibuten and that of Gly-Sar were dependent on an inwardly directed H+gradient; 2) anionic compounds such as hippurylphenyllactic acid competitively inhibited ceftibuten uptake in the presence of H+ gradient, whereas this anion did not inhibit Gly-Sar uptake; and 3) the carrier-mediated uptake of ceftibuten did not disappear even in the presence of 20 mM Gly-Sar. The results provide an evidence that several transporters with different features are potentially responsible for the uptake of β-lactam antibiotics into the intestinal cells. It is suggested that the dianionic β-lactam antibiotics that carry a net negative charge such as ceftibuten use multiple H+-dependent transport systems for absorption.
Footnotes
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Send reprint requests to: Dr. Katsumi Miyazaki, Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo 060, Japan. E-mail ken-i{at}med.hokudai.ac.jp
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↵1 Present address: Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Kami-Ikebukuro, 1–37-1, Toshima-ku, Tokyo 170 Japan.
- Abbreviation:
- BBM
- brush-border membrane
- Received May 26, 1998.
- Accepted October 27, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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