TY - JOUR T1 - Multiplicity of the H<sup>+</sup>-Dependent Transport Mechanism of Dipeptide and Anionic β-Lactam Antibiotic Ceftibuten in Rat Intestinal Brush-Border Membrane JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 66 LP - 71 VL - 289 IS - 1 AU - Ken Iseki AU - Mitsuru Sugawara AU - Kaori Sato AU - Imad Naasani AU - Tomohisa Hayakawa AU - Michiya Kobayashi AU - Katsumi Miyazaki Y1 - 1999/04/01 UR - http://jpet.aspetjournals.org/content/289/1/66.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -