Correlation of the hemodynamic and pharmacokinetic profile of intravenous milrinone in the anesthetized dog.

The relationship between the hemodynamic effects of milrinone and its plasma concentration was studied in the anesthetized instrumented dog. Milrinone was administered intravenously either as a single bolus of 10, 30 or 100 micrograms/kg or infused at a rate of 10 micrograms/kg/min. The changes in drug plasma concentration and cardiovascular parameters were determined simultaneously during the course of drug action. The intravenous bolus injections of milrinone caused dose-dependent increases in its maximum plasma concentration that resulted in concomitant increases in both cardiac contractile force and heart rate with simultaneous decreases in systolic and diastolic blood pressure. The intravenous infusion of milrinone caused parallel increases in both drug plasma concentration and cardiac contractile force; following termination of the milrinone infusion, there was a gradual decline in both its plasma concentration and in its inotropic activity, with a similar time course for these two parameters. A positive correlation (r = 0.78; p less than 0.008) was obtained between milrinone plasma concentration and its inotropic effect.