Hemodynamic effects of a new inotropic agent, piroximone (MDL 19205), in patients with chronic heart failure

The hemodynamic and neurohumoral effects of cummulative intravenous doses of piroximone (MDL 19205), a noncatecholamine, nonglycoside, imidazole derivative with positive inotropic and vasodilating properties, were studied in eight patients with severe congestive heart failure. A dose of 1.25 mg/kg in seven patients and 1.75 mg/kg in one patient increased cardiac index by 75% from 1.96 to 3.41 liters/min per m2 and decreased systemic vascular resistance (-41%), right atrial (-66%) and pulmonary wedge pressure (-35%) (all p less than 0.005). Mean arterial pressure was slightly reduced from 78 to 71 mm Hg (p less than 0.05) and forearm blood flow increased by 42%. Plasma norepinephrine decreased from 830 to 542 pg/ml (p less than 0.05) and plasma renin activity tended to increase. In four patients, dobutamine (15 micrograms/kg per min) produced a comparable increase in cardiac index (+100%), but less decrease in pulmonary wedge pressure (-21 versus -41%, p less than 0.05 versus piroximone) and, unlike piroximone, significantly increased heart rate (+22%, p less than 0.05 versus piroximone) and heart rate-blood pressure product (+30%, p less than 0.01 versus piroximone). In four other patients, a single intravenous dose of piroximone (1 mg/kg) resulted in a 35% increase in the first derivative of left ventricular pressure (dP/dt) from 796 to 1,068 mm Hg/s (p less than 0.01). Thus, piroximone is a potent inotropic agent with an acute hemodynamic profile that may be more favorable than that of dobutamine. Because the drug is orally absorbed, clinical trials of chronic efficacy are indicated.