Errors in Interpretation of Data from Equilibrium Dialysis Protein Binding Experiments

In equilibrium dialysis protein binding experiments, the fraction of free or bound drug determined at equilibrium by dialysis of a patient plasma sample does not correspond to the drug concentration in the initial plasma sample, but to the drug concentration inside the plasma compartment of the dialysis apparatus at equilibrium. That fraction of free or bound drug corresponds to a lower total drug concentration than that in the initial plasma sample because of loss of drug due to passage of free drug into the buffer compartment in the equilibrium dialysis experiment. The magnitude of the difference between the initial drug concentration and the equilibrium drug concentration depends on the extent of drug binding and experimental conditions. If the initial total drug concentration in the plasma or serum sample as well as the fraction of drug bound at equilibrium as determined by radiotracer methods are known, then, using methods given in the text, the equilibrium drug concentration, the binding parameters corresponding to equilibrium conditions, and the free drug concentration in the initial plasma sample may be estimated.