Comparative effects of gentamicin and netilmicin on Na(+)-dependent d-glucose transport in rabbit renal brush-border membrane vesicles

Abstract

The effects of gentamicin and netilmicin administration on Na(+)-dependent d-glucose transport in rabbit renal brush-border membrane vesicles (BBMV) were investigated. BBMV were isolated from rabbit kidney outer cortex (early proximal tubule) and outer medulla (late proximal tubule) 60 min after iv drug administration. Pharmacokinetics and renal accumulation of gentamicin and netilmicin were also studied. We found decreased affinity in the Na(+)-dependent d-glucose transport system after gentamicin administration only in the outer cortical preparations and not in the outer medullary ones. Gentamicin administration did not affect the membrane permeability or d-glucose distribution space of BBMV. Netilmicin had no effect on Na(+)-dependent d-glucose transport. The V(max) values of Na(+)-dependent d-glucose transport were not affected by either gentamicin or netilmicin administration in both outer cortical and outer medullary preparations. Thus, gentamicin was shown to have stronger effects on Na(+)-dependent d-glucose transport than did netilmicin. This result is consistent with the rank of nephrotoxicity for gentamicin and netilmicin. Furthermore, the Na(+)-dependent d-glucose transport system in the early proximal tubule seems to be more vulnerable to gentamicin toxicity than that in the late proximal tubule. Pharmacokinetic parameters and renal accumulation of gentamicin and netilmicin were not significantly different from each other. Thus, the difference in transport inhibition by gentamicin and netilmicin cannot be accounted for by using pharmacokinetic factors of these two drugs.