Stereoselective Effects of Disopyramide Enantiomers in Humans

Abstract

The effects of 100 mg of (S +)- and R( - )-disopyramide infused over 20 min on systolic time intervals and the QT interval were compared in five healthy volunteers. S( + )-disopyramide maximally prolonged the QTI (QT corrected for heart rate) by 10|X% (p < 0.05); R(-)-disopyramide had no effect on QTI. R(-)-disopyramide maximally prolonged the preejection period and shortened the left ventricular ejection time corrected for heart rate (PEPI and LVETI), and increased the ratio of PEP/LVET by 32, 6, and 52|X%, respectively; S( + )-disopyramide maximally increased PEPI and PEP/LVET 15 and 20|X%, respectively (p < 0.05), and had no effect on LVETI. These data suggest that the electrophysiologic effects of disopyramide enantiomers are different, and that S( + )-disopyramide has a less negative inotropic effect than R( - )-disopyramide. Changes in response were fitted to a pharmacokinetic-pharmacodynamic model, which estimated that 72|X% of the negative inotropic effects associated with racemic disopyramide may be avoided by using S( + )-disopyramide.