The Inhibitory Effects of Cephalosporin and Dipeptide on Ceftibuten Uptake by Human and Rat Intestinal Brush-border Membrane Vesicles

Abstract— 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 K_m and V_max values of 0·35 min 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.