Verbeeck R K, Gerkens J F, Wilkinson G R, Branch R A
J Pharmacol Exp Ther. 1981 Mar;216(3):479-83.
To assess the role of the liver in the elimination of furosemide, the disposition kinetics of the diuretic after intravenous administration were studied in dogs with total devascularization of the liver and sham-operated animals. Functional hepatectomy caused no significant changes in either the renal or the nonrenal clearances of furosemide; renal = 124.2 +/- 27.1 (mean +/- SE) and 106.6 +/- 17.5 ml/min and nonrenal = 148.2 +/- 11.4 and 112.6 +/- 21.0 ml/min in sham-operated and hepatectomized dogs, respectively. Devascularization of the liver had no effect on the plasma binding of furosemide which was 90.0% in the sham-operated and 88.2% in the hepatectomized animals. The steady-state volume of distribution of furosemide was relatively small, 0.70 +/- 0.09 liters/kg in control dogs and hepatectomy resulted in a reduction in this volume (0.58 +/- 0.09 liters/kg). This indicates that the liver is a significant organ for distribution of furosemide in the dog. Urinary recoveries of parent drug (43.2% of the dose in sham-operated dogs ad 49.1% in hepatectomized animals) and of its glucuronide (4.3% in sham-operated and 5.5% in hepatectomized dogs) were not influenced by hepatic devascularization. These findings demonstrate that, although nonrenal clearance accounts for about 50% of the elimination of furosemide, the liver does not play a significant role in this process in the dog.
为评估肝脏在呋塞米消除过程中的作用，在肝脏完全去血管化的犬和假手术动物中研究了静脉注射利尿剂后的处置动力学。功能性肝切除对呋塞米的肾清除率或非肾清除率均无显著影响；假手术犬和肝切除犬的肾清除率分别为124.2±27.1（均值±标准误）和106.6±17.5 ml/min，非肾清除率分别为148.2±11.4和112.6±21.0 ml/min。肝脏去血管化对呋塞米的血浆蛋白结合率没有影响，假手术动物中为90.0%，肝切除动物中为88.2%。呋塞米稳态分布容积相对较小，对照犬为0.70±0.09升/千克，肝切除导致该容积减小（0.58±0.09升/千克）。这表明肝脏是犬体内呋塞米分布的重要器官。母体药物的尿回收率（假手术犬中为给药剂量的43.2%，肝切除动物中为49.1%）及其葡糖醛酸结合物的尿回收率（假手术犬中为4.3%，肝切除犬中为5.5%）不受肝脏去血管化的影响。这些研究结果表明，虽然非肾清除率约占呋塞米消除的50%，但肝脏在犬体内的这一过程中并不起重要作用。
