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When amikacin was administered to Fischer rats at a dose of 120 mg/kg/day for up to 14 days, renal proximal tubule cells became vacuolated, but BUN and creatinine remained normal. Renal cortical drug levels rose steadily throughout the treatment period. When, in a second trial of the same duration, the drug dose was tripled, focal proximal tubular necrosis, then regeneration, occurred and the animals became azotemic. Tissue drug concentrations peaked and began to decline during the treatment period, having reached levels more than three times higher than achieved at the lower dose. Ultrastructural changes were similar to those observed with other aminoglycosides. The results indicate that amikacin is less nephrotoxic than gentamicin and more toxin than tobramycin and netilmicin in the Fischer rat.
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