Concentration-response relationships of disopyramide in patients with ventricular tachycardia

The protein binding of disopyramide is altered when concentration is increased within the therapeutic range. A wide range of free concentrations may be produced at a given total concentration. The present study assessed whether intracardiac electrophysiologic responses to disopyramide related better to free or to total concentration. Intravenous infusions of disopyramide were evaluated in 17 patients with inducible sustained ventricular tachycardia. The first maintenance infusion produced total serum concentrations of 11.7 +/- 2 mumols/L, and no significant increase occurred at higher-dose infusions. However, free concentrations during the first and second maintenance infusions were significantly different at 5.3 +/- 1 mumols/L and 6.8 +/- 1 mumols/L, respectively. Free fraction also increased significantly, from 45% +/- 8% to 50% +/- 7%. Overall change in QTc interval and ventricular tachycardia cycle length correlated with free concentration but not with total concentration. This study showed that some intracardiac measurements correlate with free concentration but that none correlate with total concentration.