Factors affecting the binding of disopyramide to serum proteins

We investigated the influence of the following factors on the binding of disopyramide to serum proteins: method of drug quantification [enzyme immunoassay (EMIT) compared with liquid chromatography (HPLC)], separation technique (ultrafiltration vs equilibrium dialysis), temperature, pH, and total concentration of disopyramide. EMIT and HPLC measurements of disopyramide in ultrafiltrates prepared from 50 sera agreed well: EMIT = 1.046 HPLC + 0.042, (r = 0.928, SEE = 0.04 mg/L). Free disopyramide concentrations in ultrafiltrates of dialyzed sera were similar to those measured in the corresponding dialysates by the EMIT method for 30 patients' sera: ultrafiltrate of serum retentate = 1.053 dialysate + 0.042. Concentrations of free [14C]disopyramide were little affected by temperature. The concentration of free disopyramide decreased as the pH was increased from 7.0 to 7.8. The concentration of free disopyramide, as determined by ultrafiltration, is strongly and directly related to total drug concentration. In the sera of 50 cardiac patients receiving chronic therapy with disopyramide and with total disopyramide concentrations of 0.5 to 5.8 mg/L, the proportion of free disopyramide ranged from 16 to 54%.