ENHANCEMENT OF TOBRAMYCIN BINDING TO RAT RENAL BRUSH-BORDER MEMBRANE BY VANCOMYCIN

Effects of vancomycin (VCM) on tobramycin (TOB) binding to rat renal b rush border membrane were examined by using isolated brush border memb rane vesicles. The binding of TOE to the membrane vesicle was enhanced by the preincubation of the vesicle with VCM. The Scatchard analysis showed that this enhancement was due mainly to the increase in the num ber of binding sites, D-Glucose uptake was not affected by VCM, which suggests that the vesicles were not damaged by VCM. The binding of spe rmine, a typical polycationic compound, to the membrane vesicles also was increased by VCM treatment, and this also was because of the incre ase in the number of binding sites. These results suggested that the e nhanced binding of these cationic compounds by VCM was due to the chan ge in the negative charge on the membrane surface. Considering that th e binding of aminoglycosides to brush border membranes is the initial step for the renal accumulation followed by the aminoglycosides-induce d nephrotoxicity, this enhancement of TOB binding to the membrane by V CM may be one of the reasons for the enhanced TOB nephrotoxicity by VC M, which has often been reported in experimental animals and patients.