Pharmacokinetics and pharmacodynamics of milrinone in chronic congestive heart failure

The acute hemodynamic effects and pharmacokinetics of bolus intravenous milrinone administration were assessed in 13 patients with severe congestive heart failure. Serial hemodynamics were measured and blood samples were obtained to determine plasma milrinone concentration and calculation of pharmacokinetic variables after administration of milrinone at 12.5, 25, 50 and 75 micrograms/kg, allowing at least 6 hours to elapse between consecutive milrinone doses. At each dose milrinone effected prompt but very short-lived increases in cardiac output and left ventricular stroke work and decreases in pulmonary artery pressure, right atrial pressure and systemic and pulmonary vascular resistance in a non-dose-dependent fashion. Pulmonary artery wedge pressure decreased in a dose-related manner. Heart rate increased significantly after the 75-micrograms/kg dose and mean arterial pressure decreased significantly only after the 50- and 75-micrograms/kg milrinone dose. The time-dependent decline in plasma milrinone concentration was biexponential and log linear, conforming to an open 2-compartment model of drug distribution and elimination. Mean plasma milrinone clearance (+/- standard error) was 0.15 +/- 0.03 liters/min/kg, volume of distribution was 0.35 +/- 0.02 liters/kg and mean elimination half-life was 1.7 hours.