Age-dependent nephrotoxicity and the pharmacokinetics of gentamicin in rats.

The pharmacokinetics and nephrotoxicity of gentamicin were studied in female Wistar rats of different ages. I.m. administration of 5 mg of gentamicin/kg revealed that young rats (90 g) had lower peak serum levels and a prolonged elimination half-life, when compared with adult animals. After repeated injections, renal gentamicin concentrations were continuously lower in young rats during the entire experiment until the 20th day after the last dose. Nephrotoxicity, as measured by urinary excretion rates of tubular cells and malic dehydrogenase, was most pronounced in the old rats (260 g) and distinctly less in the 210 g animals. The young rats reacted with a slight but not significant increase in cellular and enzyme excretion. Since one cause of nephrotoxicity can be assumed to be intrarenal accumulation of gentamicin, it may be concluded that a deficient ability to concentrate aminoglycosides in the kidneys resulted in decreased nephrotoxic potential of gentamicin in the young rats.