Author:
Brion N,Barge J,Godefroy I,Dromer F,Dubois C,Contrepois A,Carbon C
Abstract
The role of the tubular reabsorption of aminoglycosides in nephrotoxicity was considered. The tubular reabsorption rate, fractional reabsorption, and net balance, expressed as the excreted to infused aminoglycoside ratio, were concomitantly studied in male rabbits by continuous infusion of gentamicin, netilmicin, dibekacin, and amikacin. Aminoglycoside nephrotoxicity was evaluated by creatinine levels in serum and pathological renal damage after 14 days of a low- or high-dose regimen, comprising either eight, hourly intramuscular injections of gentamicin, netilmicin, or dibekacin (4 mg/kg) or amikacin (16 mg/kg); twelve, hourly intramuscular injections of gentamicin, netilmicin, or dibekacin (15 mg/kg) or amikacin (60 mg/kg); or injections of saline for the control group. Aminoglycosides exhibited three degrees of tubular reabsorption: gentamicin had the highest, netilmicin had the lowest, and dibekacin and amikacin had intermediate degrees of reabsorption. Nephrotoxicity associated with alteration in renal histology was observed with gentamicin and, to a lesser extent, with dibekacin in the high-dose regiment. No nephrotoxicity was noted with netilmicin or amikacin compared with the control group. Concentrations of the aminoglycosides in renal cortex and serum were not predictive of renal toxicity. Except for amikacin, which appeared to exhibit the lowest intrinsic renal toxicity, nephrotoxicity was correlated with the tubular reabsorption of each aminoglycoside. It was concluded that aminoglycoside renal toxicity can be determined by two major factors: importance of transport into tubular cells and intrinsic intracellular toxicity.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference28 articles.
1. Aminoglycoside accumulation kinetics in rat renal parenchyma;Aronoff G. R.;Antimicrob. Agents Chemother.,1983
2. Effect of basic amino acids and aminoglycosides on 3H-gentamicin uptake in cortical slices of rat and human kidney;Bennett W. M.;J. Lab. Clin. Med.,1982
3. The influence of dosage regimen on experimental gentamicin nephrotoxicity: dissociation of peak serum levels from renal failtire. 1;Bennett W. M.;Infect. Dis.,1979
4. Effects of furosemide on extravascular diffusion, protein binding and urinary excretion of cephalosporins and aminoglycosides in rabbits;Carbon C.;J. Pharmacol. Exp. Ther.,1980
5. Inhibition of Iysosomal phospholipases by aminoglycoside antibiotics: in vitro comparative studies;Carlier M. B.;Antimicrob. Agents Chemother.,1983
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