The inhibitory effects of cephalosporin and dipeptide on ceftibuten uptake by human and rat intestinal brush-border membrane vesicles.
The types of inhibitory effects caused by compound V (an analogue of ceftibuten) and alanylproline (dipeptide) on the uptake of ceftibuten by brush-border membrane vesicles (BBMV) prepared from human and rat small intestine were analysed. In the presence of an inward H(+)-gradient, the initial uptake rate of ceftibuten by both human and rat intestinal BBMV was concentration-dependent with apparent Km and Vmax values of 0.35 mM and 2.052 nmol (mg protein)-1 min-1 for human BBMV, and 0.50 mM and 3.056 nmol (mg protein)-1 min-1 for rat BBMV, respectively. For both human and rat BBMV, kinetic analysis by Dixon and Lineweaver-Burk plots demonstrated that the uptake of ceftibuten was competitively inhibited by compound V, whereas inhibition by alanylproline was noncompetitive or partially competitive. These results suggest that there is a stereospecific transport system which is common to ceftibuten and compound V, and that this system is not identical to the carrier system for the dipeptide, alanylproline.
Sugawara
M
M
Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Sapporo, Japan.
Toda
T
T
Kobayashi
M
M
Iseki
K
K
Miyazaki
K
K
Shiroto
H
H
Uchino
J
J
Kondo
Y
Y
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D000077722:Ceftibuten; D002511:Cephalosporins / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012588:Scintillation Counting
C091373:7-(2-(2-amino-4-thiazolyl)--4-carboxy-2-butenoylamino)-3-vinyl-3-cephem-4-carboxylic acid; D002511:Cephalosporins; D004151:Dipeptides; C038123:alanylproline; D000077722:Ceftibuten