Endogenous ligand(s) decrease drug--protein binding in uremic sera: a fluorescence probe study.

Human serum albumin (HSA) was isolated and purified (greater than 97% purity) from normal sera, from sera of patients with severe chronic renal insufficiency and from sera to which a strongly protein bound acidic drug--clofibrinic acid--was added as a model ligand. The binding properties were evaluated using dansylglycine as a fluorescent probe. Data were analyzed according to Scatchard, the binding constants were calculated by least square approximation. The binding of dansylglycine to HSA from uremic sera was substantially decreased, reflected mainly by a lower product n1 . K1, as was the binding of dansylglycine to HSA from model sera containing clofibrinic acid. The binding was restored to almost normal when HSA was treated with charcoal. It is concluded that the impaired binding of many mostly acidic drugs to HSA in uremia is due to the presence of endogenous ligands. In addition a minor contribution by changes in HSA structure cannot be excluded.