Plasma Protein Binding of Disopyramide by Equilibrium Dialysis and Ultrafiltration

Abstract

Summary An ultrafiltration technique, using Ultrafree Anticonvulsant Drug Filters, was compared to equilibrium dialysis for the determination of disopyramide plasma protein binding. Mean total recovery of drug was 92.4% for ultrafiltration compared with 98.4% for equilibrium dialysis. At initial plasma concentrations spanning the therapeutic range (2–8 μg/ml), the percentage binding of disopyramide was concentration dependent for both methods (78–38%). Initial experiments with ultrafiltration (1 ml of plasma) indicated a small (0.14%) but variable loss of total plasma protein in the ultrafiltrate (0.1-ml volume). In ultrafiltration, percentage binding of disopyramide was similar at 22 and 37°C, whereas in equilibrium dialysis, binding was significantly (p < 0.001) greater (1.4–2.7%) at 22 than at 37°C. Percentage binding for plasma (1-ml volume), assessed at ultrafiltrate volumes of approximately 0.1 and 0.25 ml, was found to be significantly (p < 0.05) different, but in practical terms the mean difference was <1% at any of the concentrations studied and was therefore of little consequence. Absolute values for percentage disopyramide bound by ultrafiltration and equilibrium dialysis were very similar, irrespective of the temperature. However, when these values were related in the usual way to the starting plasma drug concentration for ultrafiltration or to the final dialysed plasma concentration, ultrafiltration gave results that were consistently greater than those with equilibrium dialysis. Reasons for these differences and their implications are discussed.