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Research ArticleArticle

Multiplicity of the H+-Dependent Transport Mechanism of Dipeptide and Anionic β-Lactam Antibiotic Ceftibuten in Rat Intestinal Brush-Border Membrane

Ken Iseki, Mitsuru Sugawara, Kaori Sato, Imad Naasani, Tomohisa Hayakawa, Michiya Kobayashi and Katsumi Miyazaki
Journal of Pharmacology and Experimental Therapeutics April 1999, 289 (1) 66-71;
Ken Iseki
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Mitsuru Sugawara
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Kaori Sato
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Imad Naasani
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Tomohisa Hayakawa
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Michiya Kobayashi
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Katsumi Miyazaki
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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

  • 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

  • ↵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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Journal of Pharmacology and Experimental Therapeutics: 289 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 289, Issue 1
1 Apr 1999
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Research ArticleArticle

Multiplicity of the H+-Dependent Transport Mechanism of Dipeptide and Anionic β-Lactam Antibiotic Ceftibuten in Rat Intestinal Brush-Border Membrane

Ken Iseki, Mitsuru Sugawara, Kaori Sato, Imad Naasani, Tomohisa Hayakawa, Michiya Kobayashi and Katsumi Miyazaki
Journal of Pharmacology and Experimental Therapeutics April 1, 1999, 289 (1) 66-71;

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Research ArticleArticle

Multiplicity of the H+-Dependent Transport Mechanism of Dipeptide and Anionic β-Lactam Antibiotic Ceftibuten in Rat Intestinal Brush-Border Membrane

Ken Iseki, Mitsuru Sugawara, Kaori Sato, Imad Naasani, Tomohisa Hayakawa, Michiya Kobayashi and Katsumi Miyazaki
Journal of Pharmacology and Experimental Therapeutics April 1, 1999, 289 (1) 66-71;
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