[动物实验中不同氨基糖苷潜在肾毒性的分化]。

Advances in clinical pharmacology Pub Date : 1978-01-01
K Sack, H Freiesleben, B Züllich, H Beck, E Schulz
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引用次数: 0

摘要

不同氨基糖苷类动物肾毒性的实验分化。动物实验表明,定性形态学研究表明,所有氨基糖苷类均可引起类似的毒性小管和肾小球损伤。庆大霉素、妥布霉素、西索霉素、卡那霉素、卡南霉素、阿米卡星和丁胺素在大鼠肾小管肾毒性方面的定量差异可通过对大鼠肾小管细胞排泄率和尿酶的评估来证明。通过这种方法,发现剂量-效应关系导致每种抗生素可重复的不同毒性阈剂量,从而在增加肾毒性的范围内。通过测定多剂量给药期间不同时间药物的肾脏累积浓度,氨基糖苷类化合物对肾脏组织的亲和力不同。在长期研究中,这对影响毒性规模的细胞和酶的排泄率产生了修饰性影响。对大鼠和豚鼠肾毒性的比较研究也得出了类似的结果。此外,一项对人类的研究表明,肾毒性的测试结果不具有物种特异性。对于人体治疗,结论是使用新的氨基糖苷比使用庆大霉素更应谨慎,以避免肾脏损害。
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[The differentiation of potential nephrotoxicity of various aminoglycosides in animal experiments].

Experimental differentiation in the animal of nephrotoxicity of various aminoglycosides. Animal experiments showed that all aminoglycosides cause similar toxic tubular and glomerular damage when investigated by qualitative morphology. Quantitative differences in tubular nephrotoxicity of gentamicin, tobramycin, sisomicin, kanamycin, kanendomycin, amikacin, and butirosin were demonstrable by evaluation of the excretion rates of tubular cells and urinary enzymes in rats. By this means dose-effect-relationships were found resulting in reproducible different toxic threshold doses for each antibiotic, and thus in a scale of increasing nephrotoxicity. The aminoglycosides differed by 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 aminoglycosides than with gentamicin in order to avoid renal damage.

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