title: Pharmacokinetics and hemodynamic effects of the phosphodiesterase III inhibitor saterinone in patients with chronic heart failure.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Charité, Humboldt-Universität zu Berlin, Schumannstrasse 20-21, 10117 Berlin, Germany. arne.kieback@charite.de
authors.forename: A G
authors.initials: AG
authors.lastname: Kieback
authors.forename: H
authors.initials: H
authors.lastname: Iven
authors.forename: K
authors.initials: K
authors.lastname: Stolzenburg
authors.forename: E
authors.initials: E
authors.lastname: Eichner
authors.forename: W
authors.initials: W
authors.lastname: Ruckdeschel
authors.forename: G
authors.initials: G
authors.lastname: Baumann
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D003402:Creatine Kinase / Q000187:drug effects / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D003971:Diastole / Q000187:drug effects; D006325:Heart Atria / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D010879:Piperazines / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011728:Pyridones / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D013223:Statistics as Topic; D013318:Stroke Volume / Q000187:drug effects; D013599:Systole / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011728:Pyridones; D003404:Creatinine; D003402:Creatine Kinase; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C058572:saterinone