Biliary excretion of ferrioxamines of varying liposolubility in perfused rat liver

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Abstract
Experiments were conducted in the isolated perfused rat liver to establish the properties which determine the excretion of a substance into the bile. The substances investigated were semisynthetic, structurally analogous derivatives of the sideramine ferrioxamine B, with different lipid-to-water partition coefficients. The greater the lipid affinity of the ferrioxamine derivatives, the more pronounced their biliary excretion and the higher their bile-to-plasma concentration ratio. The most lipophilic derivative was present in an approximately 100-fold concentration in the bile, whereas the least lipophilic derivative did not accumulate in the bile. Analysis of the excretion kinetics suggested the existence of 2 parallel transport processes: active transport by the liver parenchymal cell and passive transport by diffusion. Active transport became far more dominant than passive transport as the degree of liposolubility of the compound increased. At high plasma concentrations active transport led to saturation. The liver uptake of the ferrioxamine derivatives followed the same pattern as their biliary excretion.