Fujimura A, Sudoh T, Ebihara A
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Life Sci. 1994;55(5):367-72. doi: 10.1016/0024-3205(94)00647-4.
The present study was undertaken to examine whether there was a time-dependent change in the toxic effects of amikacin, an aminoglycoside, on renal functions. Male Wistar rats were maintained under conditions of light from 7 am to 7 pm and dark from 7 pm to 7 am. Amikacin (1.2 g/kg) was injected intraperitoneally to animals at 4 am, 10 am, 4 pm or 10 pm. Glomerular function estimated by creatinine clearance (Clcr) and tubular function estimated by urinary excretion of a loop diuretic, furosemide, which was excreted in urine mainly by tubular secretion, were determined before and 24 hours after amikacin injection. The values of these parameters were reduced by amikacin at each observation point. The magnitude of these decrements was greatest at 4 pm both for Clcr and urinary furosemide excretion. These results suggest that the toxic effects of amikacin on renal glomerular and tubular functions vary with its time of administration.
本研究旨在探讨氨基糖苷类药物阿米卡星对肾功能的毒性作用是否存在时间依赖性变化。雄性Wistar大鼠饲养于光照时间为上午7点至晚上7点、黑暗时间为晚上7点至上午7点的环境中。分别于凌晨4点、上午10点、下午4点或晚上10点给动物腹腔注射阿米卡星（1.2 g/kg）。在注射阿米卡星前及注射后24小时测定通过肌酐清除率（Clcr）评估的肾小球功能以及通过髓袢利尿剂呋塞米的尿排泄量评估的肾小管功能，呋塞米主要通过肾小管分泌排出尿液。在每个观察点，这些参数的值均因阿米卡星而降低。对于Clcr和呋塞米尿排泄量而言，这些降低幅度在下午4点时最大。这些结果表明，阿米卡星对肾肾小球和肾小管功能的毒性作用随给药时间而变化。
