Correction for Volume Shift during Equilibrium Dialysis by Measurement of Protein Concentration.

Volume shift during equilibrium dialysis produces errors in estimating the fraction of drug unbound. This study describes a method in which protein concentration in the plasma is used to correct binding data for volume shifts. Data are presented for phenytoin, a drug that does not bind to the dialysis system, and for verapamil, a drug that does. The conventional method of not correcting for volume shift, the method described previously by one of us (TNT) for a drug that does not bind to the dialysis system, and the proposed method of determining fraction unbound are compared and discussed. It is concluded that the second method is simple and can be used to determine the unbound fraction for a drug, such as phenytoin, which does not bind to the dialysis system. If a drug binds to the dialysis system, as does verapamil, the proposed method of measuring protein concentration before and after dialysis can be reliably used to correct for volume shift.