URINARY AND BILIARY-EXCRETION OF ALUMINOXAMINE AND FERRIOXAMINE IN DOGS WITH VARIOUS RENAL-FUNCTION

We assessed the pharmacokinetics of aluminoxamine and ferrioxamine in dogs with sustained intermittent bile duct ligation and either normal renal function or stable chronic renal failure. A first group of male beagle dogs were given aluminoxamine and ferrioxamine, while a second group received desferrioxamine after loading them with iron and alumin um. Only minute amounts of ferrioxamine and aluminoxamine were found i n the bile after administration of these compounds. The distribution v olume of aluminoxamine and ferrioxamine appeared to be confined to the extracellular space and their renal excretion correlated with renal f unction. Administration of desferrioxamine to iron and aluminum-loaded dogs resulted in an increased biliary ferrioxamine but negligible alu minoxamine excretion. Renal clearance of the in vivo formed ferrioxami ne and aluminoxamine in this group strongly correlated with renal func tion. Our observations indicate that biliary excretion of intravenousl y administered ferrioxamine and aluminoxamine is negligible even in re nal failure. The data presented in this study provide indirect evidenc e that desferrioxamine administration to iron- and aluminum-loaded dog s results in the intra-hepatic formation of ferrioxamine which is part ly excreted in the bile. Biliary excretion of aluminoxamine after desf errioxamine administration remained negligible.