Effect of disopyramide on left ventricular performance: the relationship of free and total concentrations of the drug and of its mono-N-dealkylated metabolite to noninvasive indices of function.

We used M-mode echocardiography and recordings of systolic time intervals to follow changes in left ventricular systolic function of 10 normal subjects during administration of 200 mg oral disopyramide every 8 h. Left ventricular function was significantly depressed (peak rate of change of dimension - 17%, p less than 0.001; mean velocity of circumferential fiber shortening - 15%, p less than 0.01; percent fractional shortening - 16%, p less than 0.05) for as long as 7 h after a dose. These changes could be correlated with those in plasma concentrations of free and total disopyramide, and of its mono-N-dealkylated metabolite (change in peak rate of change of dimension versus levels of disopyramide plus metabolite, r = -0.41, p less than 0.03; changes in ratio preejection time/ejection time versus levels of disopyramide and metabolite, r = 0.62, p less than 0.002).