Stereoselective effects of disopyramide enantiomers in humans

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% (p less than 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%, respectively; S(+)-disopyramide maximally increased PEPI and PEP/LVET 15 and 20%, respectively (p less than 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% of the negative inotropic effects associated with racemic disopyramide may be avoided by using S(+)-disopyramide.