DISPOSITION OF FUROSEMIDE IN FUNCTIONALLY HEPATECTOMIZED DOGS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 216  (3) , 479-483
Abstract
To assess the role of the liver in the elimination of furosemide, the disposition kinetics of the diuretic after i.v. administration were studied in dogs with total devascularization of the liver and sham-operated animals. Functional hepatectomy caused no significant changes in 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 l/kg in control dogs and hepatectomy reduced this volume (0.58 .+-. 0.09 l/kg). 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 and 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. Nonrenal clearance accounts for .apprx. 50% of the elimination of furosemide but, the liver does not play a significant role in this process in the dog.