EXTRAHEPATIC METABOLISM OF FRUSEMIDE IN ANESTHETIZED RABBITS

1 Frusemide is removed from the body by biotransformation and renal se cretion, but since frusemide metabolism is not altered in patients wit h hepatic cirrhosis, the role of the liver may be questioned. The aim of the study was to investigate which organs contribute to the first-p ass metabolism and systemic clearance of frusemide. 2 Groups of anaest hetized New Zealand rabbits were administered frusemide proximally (pr ox) and distally (dist) to different organs, and blood was sampled fro m the abdominal aorta. The area under frusemide plasma concentrations- time curve (AUC0-infinity) was calculated and frusemide extraction by an organ was estimated from the ratio (AUC(dist)-AUC(prox))/AUC(dist). The small intestine extracted 83% of the absorbed dose of frusemide b ut the first-pass uptake by the liver and lungs was negligible. 3 To a ssess the contribution of the intestine and the kidneys to the systemi c clearance of frusemide, it was injected into the jugular vein and bl ood was sampled proximal and distal to each organ. The kidneys extract ed 24% of frusemide circulating in the renal arteries; on the other ha nd, the ability of the intestine to extract frusemide from the systemi c circulation could not be detected. 4 The lungs did not metabolize fr usemide in vitro; the rate of metabolism of frusemide in vitro by kidn eys was similar to that estimated in the intestine, and both rates wer e faster (P < 0.05) than that observed in the liver. 5 It is concluded that in rabbits, presystemic metabolism of frusemide is carried out b y the intestine, and that systemic clearance of frusemide is mainly pe rformed by the kidneys, although other organs, such as the intestine a nd the liver, must contribute to it.