DISPLACEMENT OF ONE LIGAND BY ANOTHER CALCULATED FROM THE REVERSE DISPLACEMENT OF THE 2ND LIGAND BY THE 1ST

This paper relates a generally applicable method for calculating mean displacement of a ligand, B, by another ligand, D, when the reverse di splacement of D by B is known. The method is applied to calculating di splacement of bilirubin from binding to albumin by a drug, warfarin or ceftriaxone. A binding isotherm for the drug to albumin is drawn, as the logarithm of free drug vs total drug concentration. A second bindi ng isotherm is drawn for the drug in the presence of a certain concent ration of bilirubin. The area between the two curves, up to a given to tal drug concentration, is measured and is divided by the concentratio n of bilirubin. The antilogarithm of the ratio is equal to the geometr ic mean of the ratio of free concentrations of bilirubin in the presen ce and absence of the drug when the bilirubin concentration varies fro m zero to the given value. The calculations are verified by comparing the direct determinations of the bilirubin displacing effect of the dr ugs by peroxidase kinetics.