Protein Binding of Disopyramide and Elevated Alpha-1-Acid Glycoprotein Concentrations in Serum Obtained from Dialysis Patients and Renal Transplant Recipients

A rapid ultrafiltration technique was used to measure the free (unbound) fraction of disopyramide in serum obtained from 14 normal volunteers, 6 chronic hemodialysis patients, and 10 renal transplant recipients. The disopyramide-free fraction varied more than tenfold at a corresponding total (free plus bound) serum disopyramide concentration of 3 micrograms/ml and was related to the concentration of an acute-phase protein, alpha-1-acid glycoprotein (AAG), in patient serum. Moreover, disopyramide-free fraction values were nearly twofold lower than normal in serum specimens obtained from those renal patients and transplant recipients with corresponding AAG serum concentrations greater than 100 mg/100 ml. AAG concentrations varied tenfold in patient serum and were on average nearly three times higher than AAG concentrations in normal volunteer serum. These findings suggested that the free fraction of disopyramide and possibly other drugs which bind extensively to AAG may be lower, and the interpatient variability in drug binding may be much more pronounced in serum obtained from hemodialysis patients and transplant recipients than previously recognized.