Parabolic Equation Relating Free and Total Drug Concentrations in Cases of Nonlinear Plasma Protein Binding

In many cases of nonlinear drug-protein binding, investigators have fitted data to the classical Langmuir model with two classes of binding sites involving four parameters. For human serum albumin binding of tolmetin and salicylate, a simple two-parameter parabolic equation relating free to total concentrations fitted the binding data better. Thus, the free fraction corresponding to the serum or plasma drug concentration in the blood sample taken from a subject can be estimated directly from the parabolic model. This is not the case when the Langmuir model is used to describe nonlinear binding data since the positive root of a cubic equation must be obtained to estimate the free from the total concentration. The direct relationship between free and total drug concentrations would be useful in many clinical situations.