Distribution and renal excretion of desferrioxamine and ferrioxamine in the dog and in the rat

Abstract

In nephrectomized dogs given a single large intravenous dose of desferrioxamine the plasma concentrations declined rapidly. The decline could be described by the regression lines of three first-order reactions of which the first probably corresponds to equilibration and the second and third to metabolic degradation. The half-life of desferrioxamine in the nephrectomized dog was 76 ± 10 min. During the phase of rapid metabolic degradation metabolites of desferrioxamine accumulated in the blood. The volume of distribution of desferrioxamine in nephrectomized dogs was found to be 62.9 ± 6.7 per cent of bodyweight. Ferrioxamine was not degraded to any appreciable extent in nephrectomized dogs: after a large dose the plasma concentration fell very slowly—probably as a consequence of biliary excretion. The volume of distribution of ferrioxamine was equal to the volume of the extracellular compartment. Renal excretion of desferrioxamine in five out of six anaesthetized dogs occurred by glomerular filtration with tubular reabsorption at very low blood levels. In unanaesthetized rats desferrioxamine was excreted by glomerular filtration and tubular secretion. Tubular secretion seemed to be independent of tubular PAH secretion. Ferrioxamine was reabsorbed at low plasma levels both in anaesthetized dogs and in unanaesthetized rats: The reabsorptive process had a low Tm.