Animal experiments showed that all aminoglycosides cause similar toxic tubular and glomerular damage when investigated by qualitative morphology. Quantitative differences in the tubular nephrotoxicity of gentamicin, tobramycin, sisomicin, kanamycin, kanendomycin, amikacin, and butirosin can be demonstrated experimentally by evaluation of the excretion rates of tubular cells and urinary enzymes in rats. By this means dose-effect relationships were established resulting in varying reproduceable toxic threshold doses for each antibiotic, and thus in a scale of increasing nephrotoxicity. The aminoglycosides differed in their affinity to kidney tissue as measured by determination of the accumulating renal concentrations of the drugs at different times during multiple-dose administration. This had a modifying influence on excretion rates of cells and enzymes affecting the scale of toxicity in long-term studies. Comparative investigations on nephrotoxicity in rats and guinea pigs gave similar results. In addition, a study in man suggested that the test results of nephrotoxicity are not species-specific. For human therapy it is concluded that even more caution should be practised with the new aminoglycerides than with gentamicin in order to avoid renal damage.
The potential renal tolerance of cefuroxime was investigated in 80 female albino Wistar rats and compared with that of cephacetrile. The drugs were administered i.m. in different dosages (1000, 2000, 3000 and 5000 mg/kg/day; dosage interval: 12 h) over a period of five days. The excretion of tubular cells and urinary malic dehydrogenase was assessed before, during and after administration of the antibiotics. In addition, the concentration of serum urea was analysed and the renal histology was examined. The following toxic threshold doses were estimated: cefuroxime 5000 mg/kg/day, cephacetrile 3000 mg/kg/day. In comparison with other cephalosporines cefuroxime belongs to those antibiotics with which a high degree of renal tolerance is demonstrated.
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