Decreased drug binding in uraemia: effect of indoxyl sulphate and other endogenous substances on the binding of drugs and dyes to human albumin.

Ten uraemic metabolites, alone or in combination, have been investigated by equilibrium dialysis for their effect on the binding of methyl red, methyl orange, 2-(4'-hydroxybenzeneazo)benzoic acid (HABA), phenytoin and L-tryptophan to human albumin (HSA). Indoxyl sulphate emerges as a substance likely to inhibit binding in vivo while the other metabolites were unlikely to be implicated in the binding defect of uraemic plasma. The effects of indoxyl sulphate, on the binding of HABA and methyl red, studied by equilibrium dialysis and spectroscopy respectively, indicated competitive inhibition. The results suggest that indoxyl sulphate and indole carboxylic acids may contribute to the binding defect of uraemic plasma.