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氨基糖苷类肾毒性的预测(作者译)

[Prediction of aminoglycoside nephrotoxicity (author's transl)].

作者信息

Whelton A

出版信息

Nouv Presse Med. 1978 Nov 29;7(42):3838-43.

PMID:714689
Abstract

The intrarenal distribution characterisitcs of tobramycin were evaluated in 76 normal canine kidneys during various states of hydration and urine pH. The intrarenal gradient paterns of the drug were also evaluated in 18 severely diseased kidneys obtained from 14 patients undergoing pre-transplant nephrectomy. The results were compared with our 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 less than 0.05), medulla (p less than 0.01) and papilla (p less than 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.

摘要

在76只正常犬肾处于不同水合状态和尿液pH值时,评估了妥布霉素的肾内分布特征。还对14例接受移植前肾切除术患者的18只严重病变肾脏进行了该药物的肾内梯度模式评估。将结果与我们早期评估庆大霉素在54只健康犬肾和12只病变人肾中蓄积特征的数据进行了比较。在妥布霉素研究中,具有潜在肾毒性重要性的肾皮质药物蓄积显著较低。同样,妥布霉素的皮质组织结合率为59%(±标准误4),庆大霉素为85%(±标准误3)。严重疾病的存在显著降低了两种化合物的肾药物浓度。然而,在这些组织中,妥布霉素在肾皮质(p<0.05)、髓质(p<0.01)和乳头(p<0.01)中的组织浓度略高于庆大霉素。结果表明,在健康和疾病状态下,妥布霉素和庆大霉素的肾处置存在重要差异,这与毒理学和治疗学重要性问题相关。

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