Nephrotoxicity of gentamicin. Action on subcellular organelles and pharmacokinetics in the kidney.

Our findings on the renal pharmacokinetics of gentamicin explain why: (1) gentamicin concentrations in the kidney reach levels high enough to provoke injuries to the organelles; (2) the morphological manifestations of toxicity involve primarily the convoluted proximal tubule (which constitutes the largest part of the cortex), since antibiotic concentrations in this area are especially high; (3) nephrotoxicity is related to duration of treatment; (4) urine may contain small quantities of gentamicin up to 3 weeks after the end of therapy (14, 22, 30); (5) nephrotoxicity continues after discontinuance of the treatment, and (6) the hepatocytes, whose lysosomes are very sensitive to the action of gentamicin, show no obvious signs of toxicity, since the antibiotic never attains a high enough concentration in this organ.