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

Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8200291 Publication Model: Print Cited Medium: Print ISSN: 0167-5273 (Print) Linking ISSN: 01675273 NLM ISO Abbreviation: Int J Cardiol Subsets: MEDLINE

Publication: Amsterdam : Elsevier
Original Publication: Amsterdam : Elsevier/North-Holland Biomedical Press, c1981-

3',5'-Cyclic-AMP Phosphodiesterases/*antagonists & inhibitors ; Heart Failure/*drug therapy ; Heart Failure/*physiopathology ; Phosphodiesterase Inhibitors/*pharmacokinetics ; Phosphodiesterase Inhibitors/*therapeutic use ; Piperazines/*pharmacokinetics ; Piperazines/*therapeutic use ; Pyridones/*pharmacokinetics ; Pyridones/*therapeutic use; 3',5'-Cyclic-AMP Phosphodiesterases/metabolism ; Adult ; Aged ; Blood Platelets/drug effects ; Blood Platelets/metabolism ; Blood Pressure/drug effects ; Chronic Disease ; Creatine Kinase/drug effects ; Creatine Kinase/metabolism ; Creatinine/urine ; Cyclic Nucleotide Phosphodiesterases, Type 3 ; Diastole/drug effects ; Heart Atria/drug effects ; Heart Failure/metabolism ; Heart Rate/drug effects ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Phosphodiesterase Inhibitors/metabolism ; Piperazines/metabolism ; Pyridones/metabolism ; Statistics as Topic ; Stroke Volume/drug effects ; Systole/drug effects ; Time Factors ; Treatment Outcome ; Vascular Resistance/drug effects

Unlabelled: 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.

0 (Phosphodiesterase Inhibitors)
0 (Piperazines)
0 (Pyridones)
AYI8EX34EU (Creatinine)
EC 2.7.3.2 (Creatine Kinase)
EC 3.1.4.17 (3',5'-Cyclic-AMP Phosphodiesterases)
EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 3)
W4P85FO7GS (saterinone)

Date Created: 20031016 Date Completed: 20040427 Latest Revision: 20190816

20231215

10.1016/s0167-5273(03)00030-5

14559131