Pharmacokinetics and hemodynamic effects of the phosphodiesterase III inhibitor saterinone in patients with chronic heart failure

The introduction of PDE III-inhibitors has been a major innovation for the intravenous drug treatment of patients suffering from heart failure. In this study, the pharmacokinetics and hemodynamic effects of the PDE III-inhibitor saterinone were examined in twelve male patients with severe chronic heart failure.

Methods: Saterinone was given by intravenous infusion for 24 hours at a rate of 1.5 microg/kg per min. According to a standardized protocol, blood samples were drawn for measurement of saterinone plasma levels and hemodynamic measurements were taken in order to analyze the correlation between plasma levels and hemodynamic effects.

Results: The correlation coefficient between the increase in cardiac index and the logarithms of saterinone plasma concentrations was r=0.827 (p=0.003). Between the logarithms of plasma concentrations and the decrease in pulmonary capillary wedge pressure a correlation coefficient of r=0.964 (p<0.001) was calculated for the first twelve hours of saterinone infusion. The decrease of saterinone plasma concentrations can be fitted to a three-compartment-model (half-lifes were 4.24 minutes for the alpha-phase, three hours for the beta-phase and 15.7 hours for the terminal phase). Saterinone induced maximal increases of 56.6% in cardiac index, 48.9% in stroke volume index, 28.4% in heart rate and maximal decreases of 17.3% in mean systemic blood pressure, 38.4% in mean pulmonary artery pressure, 74.2% in right atrial pressure, 46.9% in pulmonary capillary wedge pressure, 39.9% in systemic vascular resistance and 71.8% in pulmonary vascular resistance.

Conclusion: Saterinone was demonstrated to be a safe, potent drug during an intravenous infusion over 24 hours at a rate of 1.5 microg/kg per min.