Behavior of Amikacin in Renal Parenchyma of Normal Rats and of Rats with Acute Obstructive Renal Insufficiency

Abstract

Aminoglycosides show a remarkable tendency to accumulate and persist in the renal parenchyma. In order to study the kinetics of this phenomenon for amikacin, rats received 25 mg/kg of this antibiotic i.p. and were sacrificed in groups of 6 up to 15 days after the injection. At 6 h, while the other organs and the serum were almost completely freed of amikacin, concentrations in the renal cortex reached 156 ± 21 µg/g, or 6 times the peak serum level (instead of 20 times the peak serum level for gentamicin or sisomicin, a difference which is reduced by the fact that amikacin is given in higher dosage). They then decreased very slowly, according to a half-life of 122 h. Although it decreases glomerular filtration, ligation of ureters 20 h before the injection quadrupled the concentration in the cortex. These data explain the characteristics of the nephrotoxicity of amikacin and the increased toxic risk in acute obstructive renal insufficiency.