INHIBITORY EFFECTS OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS ON CEFROXADINE UPTAKE BY RABBIT SMALL-INTESTINAL BRUSH-BORDER MEMBRANE-VESICLES

Effects of angiotensin-converting enzyme (ACE) inhibitors, captopril, enalapril maleate and quinapril, on the uptake of aminocephalosporin a ntibiotic, cefroxadine, by rabbit small intestinal brush border membra ne vesicles were examined. These ACE inhibitors significantly inhibite d the uptake of cefroxadine, which is transported by H+/dipeptide tran sporter in the membrane, in the order of captopril < enalapril < quina pril in the presence of an inward H+ gradient. Inhibitory effect of qu inapril was more marked than that of aminocephalosporin cephradine, wh ile in the absence of an inward H+ gradient inhibition by these ACE in hibitors was much less. Dixon plot analysis showed that the inhibition by enalapril and quinapril in the presence of an inward H+ gradient o ccurred in a competitive manner and estimated inhibition constants of these two drugs to be 5.3 mM and 0.46 mM, respectively. These results suggested the strong affinity of these ACE inhibitors, especially quin april, on the H+/dipeptide transporter.