Hottendorf G H, Barnett D, Gordon L L, Christensen E F, Madissoo H
Antimicrob Agents Chemother. 1981 Jun;19(6):1024-8. doi: 10.1128/AAC.19.6.1024.
Nephrotoxicity comparisons of aminoglycosides in rats, utilizing large multiples of human doses, have indicated an advantage for netilmicin. However, no nephrotoxicity advantage of netilmicin has been demonstrated at the lower doses used in clinics. Some high-dose studies in rats have also suggested that the slope of the nephrotoxicity dose-response curve of netilmicin was less steep than the slopes of other aminoglycosides. Therefore, the slopes of the nephrotoxicity dose-response curves of gentamicin, amikacin, and netilmicin were compared in 200 rats at low multiples (one to five times) of human clinical doses. Histopathological evaluations of both kidneys from each rat revealed that netilmicin produced equivalent or greater nephrotoxicity as compared with gentamicin and amikacin and that the slope of the nephrotoxicity dose-response curve of netilmicin was approximately one-half as steep as the slopes of amikacin and gentamicin, which were parallel. The distribution of casts excreted in the urine after 2 weeks of dosing and the terminal gross observations corroborated the flatter dose-response slope of netilmicin. Nephrotoxicity advantages predicted by high-dose comparisons with netilmicin in rats are apparently a function of its less steep dose-response slope and therefore may have no relevance to lower doses.
在大鼠中使用数倍于人体剂量对氨基糖苷类药物进行肾毒性比较，结果显示奈替米星具有优势。然而，在临床使用的较低剂量下，奈替米星并未显示出肾毒性优势。一些在大鼠中的高剂量研究还表明，奈替米星肾毒性剂量-反应曲线的斜率比其他氨基糖苷类药物的斜率更平缓。因此，在200只大鼠中，以人体临床剂量的低倍数（1至5倍）比较了庆大霉素、阿米卡星和奈替米星肾毒性剂量-反应曲线的斜率。对每只大鼠的双肾进行组织病理学评估发现，与庆大霉素和阿米卡星相比，奈替米星产生的肾毒性相当或更大，且奈替米星肾毒性剂量-反应曲线的斜率约为平行的阿米卡星和庆大霉素曲线斜率的一半。给药2周后尿液中排出管型的分布以及末次大体观察结果证实了奈替米星剂量-反应曲线较平缓。在大鼠中通过与奈替米星进行高剂量比较所预测的肾毒性优势显然是其剂量-反应曲线斜率较平缓的结果，因此可能与较低剂量无关。
