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  • Title: Correlation between renal membrane binding and nephrotoxicity of aminoglycosides.
    Author: Williams PD, Bennett DB, Gleason CR, Hottendorf GH.
    Journal: Antimicrob Agents Chemother; 1987 Apr; 31(4):570-4. PubMed ID: 3606061.
    Abstract:
    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.
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