庆大霉素给药间隔与豚鼠耳、肾毒性的关系  

The relation between single or multiple dose gentamycin daily and nephrotoxicity and ototoxicity in guinea pigs

作　　者：刘皋林[1] 盛海峰[1] 邓渝林[1] 鲍晓梅[1] 史秀凤[2] 梁振福[2] 叶煦亭[3] 

机构地区：[1]第二军医大学长征医院药学部,上海200003 [2]海军医学研究所神经生理学研究室 [3]第二军医大学基础医学部细胞生物学教研室

出　　处：《第二军医大学学报》2001年第1期61-64,共4页Academic Journal of Second Military Medical University

摘　　要：目的 :研究庆大霉素 (Gen)单剂量和多剂量给药与耳、肾毒性作用之间的相关性。 方法 :32只豚鼠随机分成生理盐水对照 (C)组、单剂量 (S)组 (Gen,12 0 m g/ kg,1次 / d)、多剂量 (M)组 (Gen,6 0 m g/ kg,2次 / d)。应用 SC-声刺激器、听觉脑干诱发电位 (ABR)检测及对耳蜗、近端肾小管上皮细胞的线粒体、肾小球基底膜等电镜观察 ,研究豚鼠电生理和组织学改变。应用荧光偏振免疫法检测不同时间血液中及实验后期外淋巴液中的药物浓度。结果 :生理测定 (如耳廓反射、ABR)、病理切片和电镜扫描观察表明 :(1)与 C组相比 ,S组和 M组均造成一定程度的耳、肾损伤 ,M组的毒性明显大于 S组 (P<0 .0 5 ) ,但随着用药天数的增加 ,S组动物的毒性逐日增强。 (2 ) S组与 M组动物 10 h后血清 Gen浓度分别为 3.0 4和 3.5μg/ m l,而同一时间测得的外淋巴液中浓度分别高达 2 6 .42和 2 6 .3μg/ ml。 结论Objective: To compare nephrotoxicity and ototoxicity of gentamycin administered in single dose or multiple dose daily in guinea pigs. Methods: Thirty two male guinea pigs were divided into physiological saline control, single dose group daily (gentamycin, 120 mg/kg, 1/d) and multiple dose group daily (gentamycin, 60 mg/kg, 2/d). The physiopathology of renal and cochlea in guinea pigs were examined using auditory brainstem response (ABR), SC sound irritation and electron microscope. The gentamycin concentrations in serum and in perilymph were monitored by fluorescene polarization immunoassay (FPIA). Results: (1) Compared with control group, both gentamycin single and mulitiple daily doses injuried kidney and cochlea to some extent.The injury of multiple dose groups were worse than that the single dose groups ( P < 0.05). (2) Serum gentamycin concentrations of single and multiple dose groups after 10 h injection were 3.04 μg/ml and 3.5 μg/ml,respectively. The concentrations in perilymph were 26.42 μg/ml and 26.3 μg/ml, respectively. Conclusion: Once daily administration of gentamycin has a lower risk of ototoxicity and nephrotoxicity in early stage.

关 键 词：庆大霉素 剂量 耳毒性 肾毒性 豚鼠 给药间隔 

分 类 号：R978.12[医药卫生—药品]