Intestinal brush-border transport of the oral cephalosporin antibiotic, cefdinir, mediated by dipeptide and monocarboxylic acid transport systems in rabbits.
Intestinal absorption of the orally active cephalosporin, cefdinir, was investigated using brush-border membrane vesicles prepared from rabbit small intestine. The initial uptake of cefdinir was pH-dependent, with increased uptake at acidic pH, and was not influenced by either sodium gradient or membrane potential difference. Cefdinir uptake was saturable with an apparent Michaelis constant of 8.1 mM. Initial uptake of cefdinir was inhibited by dipeptides (glycyl-L-proline and glycylsarcosine), beta-lactam antibiotics (cephradine, cefixime and penicillin V), and monocarboxylic acids (acetic acid and L-lactic acid), whereas the uptake of cephradine and cefixime was not inhibited by monocarboxylic acids. Cefdinir significantly inhibited the initial uptake of cephradine, cefixime and [3H]acetic acid. From these results, it was suggested that cefdinir was transported across brush-border membranes by both dipeptide and monocarboxylic acid carriers.
Tsuji
A
A
Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Tamai
I
I
Nakanishi
M
M
Terasaki
T
T
Hamano
S
S
D000085:Acetates / Q000493:pharmacokinetics; D000818:Animals; D001693:Biological Transport, Active; D002264:Carboxylic Acids / Q000378:metabolism*; D000077525:Cefdinir; D020682:Cefixime; D002439:Cefotaxime / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D002511:Cephalosporins / Q000493:pharmacokinetics*; D002515:Cephradine / Q000493:pharmacokinetics; D004151:Dipeptides / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008871:Microvilli / Q000378:metabolism; D011817:Rabbits
D000085:Acetates; D002264:Carboxylic Acids; D002511:Cephalosporins; D004151:Dipeptides; D020682:Cefixime; D000077525:Cefdinir; D002515:Cephradine; D002439:Cefotaxime