Vol. 289, Issue 1, 66-71, April 1999

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

Ken Iseki, Mitsuru Sugawara, Kaori Sato, Imad Naasani¹, Tomohisa Hayakawa, Michiya Kobayashi and Katsumi Miyazaki

Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Kita-ku, Sapporo, Japan

To elucidate the transport characteristics of the H⁺/dipeptide carrier that recognizes the orally active -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 -lactam antibiotics into the intestinal cells. It is suggested that the dianionic -lactam antibiotics that carry a net negative charge such as ceftibuten use multiple H⁺-dependent transport systems for absorption.