Elliott W C, Parker R A, Houghton D C, Gilbert D N, Bennett W M
Res Commun Chem Pathol Pharmacol. 1981 Sep;33(3):419-32.
To evaluate the nephrotoxicity of the new aminoglycoside, dibekacin, relative to gentamicin, we administered both drugs in doses of 40 and 120 mg/kg per day to male and female Fischer 344 rats. At sacrifice, we determined serum creatinine, in vitro renal cortical uptake of 14C N-methyl nicotinamide and para-aminohippurate, renal cortical antibiotic concentrations, and real histology. Dibekacin and gentamicin were similar in overall toxicity. Dibekacin differed from gentamicin and other aminoglycosides (1) in failing to cause early transient stimulation of para-aminohippurate uptake in male rats and (2) in the location of histologic damage at the 120 mg/kg dose. We conclude that: 1) in this model, dibekacin is comparable to gentamicin in nephrotoxic potential, and 2) the lack of early stimulation of para-aminohippurate uptake in male rates after dibekacin treatment may be related to greater initial injury to the late proximal tubule than is caused by gentamicin.
为评估新型氨基糖苷类药物地贝卡星相对于庆大霉素的肾毒性,我们以每天40毫克/千克和120毫克/千克的剂量对雄性和雌性Fischer 344大鼠给予这两种药物。在处死时,我们测定了血清肌酐、体外肾皮质对14C N-甲基烟酰胺和对氨基马尿酸的摄取、肾皮质抗生素浓度以及肾脏组织学。地贝卡星和庆大霉素在总体毒性方面相似。地贝卡星与庆大霉素及其他氨基糖苷类药物的不同之处在于:(1)不会引起雄性大鼠对氨基马尿酸摄取的早期短暂刺激;(2)在120毫克/千克剂量时组织学损伤的部位。我们得出以下结论:1)在该模型中,地贝卡星在肾毒性潜力方面与庆大霉素相当;2)地贝卡星治疗后雄性大鼠对氨基马尿酸摄取缺乏早期刺激可能与晚期近端小管比庆大霉素引起的初始损伤更大有关。