Plasma protein binding of amiodarone in a patient population: measurement by erythrocyte partitioning and a novel glass-binding method.

1. Amiodarone is an effective antiarrhythmic drug whose therapeutic usefulness is limited by variable pharmacokinetics and considerable toxicity. Total plasma concentrations are not reliably related to therapeutic effect, but if plasma protein binding varies between patients, then free drug concentrations may provide a better measure of drug effectiveness. 2. The plasma protein binding of amiodarone was measured by erythrocyte partitioning, and found to be the same in six healthy subjects and eight patients being treated for cardiac arrhythmias (mean = 99.98%; range 99.97-99.99%). The free fraction of amiodarone was independent of the total drug concentration (r = -0.41, P greater than 0.50) and albumin level (r = -0.31, P greater than 0.50). 3. These data show no advantage in monitoring free concentrations of amiodarone. On the other hand, the patients in this study did not receive very high doses of amiodarone, and were free from drug side effects and biochemical abnormalities. Possibly a more heterogeneous group of patients would show variability in amiodarone binding. This should be examined, especially for patients with variations in alpha 1-acid glycoprotein, a major ligand for basic drugs and a likely major binding protein for amiodarone.