Chiu P J, Long J F
Antimicrob Agents Chemother. 1978 Aug;14(2):214-7. doi: 10.1128/AAC.14.2.214.
The effect of furosemide on gentamicin excretion and tissue accumulation was studied with clearance techniques in anesthetized rats, at two different infusion rates of saline or Ringer solution. Gentamicin ( approximately 20 mg/kg) was administered by constant intravenous infusion over a period of 3 h. With the low fluid infusion rate, furosemide (25 mg/kg intravenously) caused severe reduction in glomerular filtration rate and diminished urinary output of gentamicin. Serum and renal tissue levels of the antibiotic were significantly elevated. High fluid infusion prevented the decline of the glomerular filtration rate, with near normalization of all measurements. A fluid deficit incurred by furosemide was noted at both the low and high infusion rates. Complete correction of this fluid deficit by continuous adjustment of the infusion rate fully restored normal renal handling of gentamicin. These results suggest that furosemide had no direct effect on renal excretion of gentamicin. In comparison, renal handling of gentamicin in rats did not respond to changes in the rate of fluid infusion in the absence of furosemide therapy. It appears that gentamicin excretion and gentamicin accumulation in the renal cortex in furosemide-treated rats, in contrast with those in untreated rats, are influenced significantly by the rate of fluid infusion. Fluid administration sufficient to maintain the glomerular filtration rate was found to be necessary for appropriate gentamicin elimination, with consequent reduction in serum and renal tissue levels of the drug.
在麻醉大鼠中，采用清除技术研究了呋塞米对庆大霉素排泄和组织蓄积的影响，分别给予两种不同输注速率的生理盐水或林格液。庆大霉素（约20mg/kg）通过静脉恒速输注3小时给药。在低液体输注速率时，呋塞米（静脉注射25mg/kg）导致肾小球滤过率严重降低，庆大霉素尿量减少。抗生素的血清和肾组织水平显著升高。高液体输注可防止肾小球滤过率下降，所有测量值接近正常。在低输注速率和高输注速率时均观察到呋塞米引起的液体缺失。通过持续调整输注速率完全纠正这种液体缺失，可使庆大霉素的肾脏处理功能完全恢复正常。这些结果表明，呋塞米对庆大霉素的肾脏排泄没有直接影响。相比之下，在未使用呋塞米治疗的情况下，大鼠对庆大霉素的肾脏处理功能对液体输注速率的变化没有反应。与未治疗的大鼠相比，呋塞米治疗的大鼠中庆大霉素的排泄和在肾皮质中的蓄积似乎受液体输注速率的显著影响。发现给予足够的液体以维持肾小球滤过率对于庆大霉素的适当消除是必要的，从而降低药物的血清和肾组织水平。
