EFFECT OF PROTEIN-CONCENTRATION ON THE BINDING OF DRUGS TO HUMAN-SERUM ALBUMIN .1. SULFADIAZINE, SALICYLATE AND PHENYLBUTAZONE

The binding of sulfadiazine, salicylate or phenylbutazone to human plasma and human serum albumin has been studied as a function of protein concentration. Results show that, as the concentration of albumin increases, the binding of all three drugs decreases. This phenomenon does not appear to be due to the presence of endogenous-competing ligands in serum or crystalline albumin preparations. Fluorescence depolarization measurements of dansylglycine complexes with human serum albumin show no evidence for the molecular aggregation" of human serum albumin at high concentrations. Binding parameters obtained with dilute albumin solutions when extrapolated to physiological albumin concentrations may predict a higher degree of binding than that which is observed by direct measurement. The phannacokinetic implications of these findings are discussed. © 1979."