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Ipazilide fumarate is an investigational antiarrhythmic agent with Vaughan Williams class I and III actions, including prolongation of both ventricular refractoriness and action potential duration. Because of the frequent use of antiarrhythmic agents in patients with heart failure, we investigated the hemodynamic effects of oral administration of 400, 200, and 100 mg of ipazilide fumarate in 15 patients with congestive heart failure. There was a marked hemodynamic response to ipazilide, with the peak effect noted 2 hours after drug administration. In patients who received 400 mg ipazilide, the mean cardiac index was decreased by 0.5 L/min/m2 at 2 hours (p < 0.05). After 200 and 100 mg ipazilide, the decreases were a more modest 0.3 and 0.1 L/min/m2, respectively. The mean arterial pressure also decreased in a dose- and time-dependent manner, although this did not reach statistical significance for any of the doses. Left ventricular filling pressure, right atrial pressure, and heart rate were not altered by ipazilide. Plasma concentrations of ipazilide peaked 90 minutes after administration of 100 or 200 of the drug, but peak concentrations were noted 3 hours after administration of 400 mg. The hemodynamic response correlated with the plasma concentration of ipazilide determined contemporaneously. We conclude that, as with most antiarrhythmic agents, single-dose administration of ipazilide fumarate can cause clinically significant hemodynamic deterioration.