PREDICTION DE LA TOXICITE DES AMINOSIDES

The intrarenal distribution characteristics of tobramycin were evaluated in 76 normal canine kidneys during various states of hydration and urine pH. The intrarenal gradient patterns of the drug were also evaluated in 18 severely diseased kidneys obtained from 14 patients undergoing pre-transplant nephrectomy. The results were compared with the earlier data evaluating gentamicin accumulation characteristics in 54 healthy canine and 12 diseased human kidneys. Renal cortical drug accumulation, a matter of potential nephrotoxic importance was significantly lower in the tobramycin studies. Similarly, cortical tissue binding of tobramycin was 59% ( ± S.E. 4) and for gentamicin was 85% ( ± S.E. 3). The presence of severe disease drastically reduced the renal drug concentration of both compounds. However, in such tissues tobramycin demonstrated slightly higher tissue concentrations in renal cortex (p <0.05), medulla (p <0.01) and papilla (p <0.01) than those measured for gentamicin. The results indicate that there are important differences in the renal disposition of tobramycin and gentamicin in health and disease which relate to matters of toxicologic and therapeutic importance.