QTc Interval Length Research Articles

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.

Effects of bepridil, a new antianginal agent, on ambulatory electrocardiography in human volunteers.

We studied the effects of bepridil, a new antianginal agent, on the ambulatory electrocardiogram in seven human volunteers. The drug was administered in three sequential periods of 12 days separated by 24 days without treatment. Heart rate was not significantly altered at 200 mg/day, but fell from day 3 at 300 mg/day and from day 1 at 600 mg/day. Average fall in heart rate was approximately 8% at 300 mg/day and 11% at 600 mg/day (day 7). At 200 mg/day the peak plasma level was reached after 11 days of treatment (0.28 +/- 0.4 microgram/ml). At 300 mg/day, a plateau was reached on day 7 (0.44 +/- 0.04 micrograms/ml) and at 600 mg/day from day 8 (0.97 +/- 14 micrograms/ml). We found a highly significant relationship between blood concentration of bepridil and mean RR interval lengths over 24 h. The QTc interval was lengthened at all doses, but there was no significant correlation between plasma level and increase in QTc interval length.