Correlation between renal membrane binding and nephrotoxicity of aminoglycosides.
The kinetics of aminoglycoside binding to renal brush border and basolateral membrane vesicles from rat renal cortex were studied by using [3H]amikacin. [3H]amikacin binding to renal membranes was found to be a rapid, saturable process with a fourfold greater affinity for basolateral membranes than for brush border membranes (Kd basolateral = 607 microM; Kd brush border = 2,535 microM). Renal membranes prepared from immature rats (2 to 3 weeks old) exhibited a significantly lower affinity compared with membranes from adults (Kd basolateral = 2,262 microM; Kd brush border = 6,216 microM). Additionally, the inhibitory behavior of several aminoglycosides versus [3H]amikacin binding to brush border membranes revealed the following rank order of potency: neomycin greater than tobramycin approximately gentamicin approximately netilmicin greater than amikacin approximately neamine greater than streptomycin. The relative insensitivity of immature rats to aminoglycoside-induced nephrotoxicity in vivo and the comparative nephrotoxicity of the various aminoglycosides suggest that renal membrane-binding affinity is closely correlated to the nephrotoxic potential of these antibiotics.
D000617:Aminoglycosides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000633:toxicity; D001485:Basement Membrane / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents