Protein binding of disopyramide in liver cirrhosis and in nephrotic syndrome

The plasma protein binding of disopyramide (D) was determined in seven patients with cirrhosis, six with nephrotic syndrome, and seven healthy subjects. Plasma samples containing concentrations of 0.2 to 12.0 micrograms/ml were ultrafiltered and the free fractions were measured with fluorescence polarization immunoassay. The mean free fractions at D concentrations ranging from 1 to 6 micrograms/ml were significantly (P less than 0.01) greater in patients with cirrhosis than in healthy subjects. No difference was observed between patients with nephrotic syndrome and healthy subjects. The free fraction at D 3 micrograms/ml correlated better with alpha 1-acid glycoprotein (r = -0.77) than with albumin (r = -0.46). Patients with cirrhosis had significantly (P less than 0.01) lower capacity constants as compared with the other two study groups. There was a significant (P less than 0.01) correlation between capacity constant and alpha 1-acid glycoprotein (r = 0.71). Our results suggest that the D therapeutic range measured as the total plasma concentration in cirrhosis, but not in nephrosis, should be approximately 50% lower than previously believed.