title: Hemodynamic effects and concentration-effect relationship of a graded infusion of piroximone in patients with severe heart failure.
abstract: Piroximone is a new phosphodiesterase III inhibitor that combines inotropic and vasodilator properties. To elucidate the optimal dose regimen and the dose-concentration-effect relationships, we studied eight patients with congestive heart failure of New York Heart Association class IV during a continuous multistage infusion over a 24-h period followed by a 4-h washout. After a bolus of 0.5 mg/kg, infusions at a rate of 2.5, 5.0, and 10.0 micrograms/kg/min for 8 h each were given to determine the maintenance dose of piroximone required to achieve an increase in cardiac index > or = 30%. Serial assessment of hemodynamics, plasma piroximone levels, and ventricular ectopic beats was performed. Following the loading dose and at higher infusion rates (5 and 10 micrograms/kg/min) Piroximone produced significant hemodynamic changes compared to baseline, i.e., a maximum increase in cardiac index from 2.2 +/- 0.4 to 3.6 +/- 0.8 L/min/m2 (67 +/- 21%), decreases in right atrial pressure from 14 +/- 3 to 9 +/- 3 mm Hg (40 +/- 16%), pulmonary capillary wedge pressure from 29 +/- 5 to 23 +/- 7 mm Hg (28 +/- 18%), pulmonary vascular resistance from 249 +/- 93 to 151 +/- 59 (45 +/- 19%), and systemic vascular resistance from 1,330 +/- 442 to 752 +/- 272 dyn s/cm5 (44 +/- 19%). Piroximone increased the heart rate by 10% at the highest dose and produced a decrease in mean arterial pressure by 13%. There was a slight increase in ventricular ectopy in two patients (2.2 and 3 VPBs/min) and no change in the remaining six.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Cardiology, University Hospital, Zurich, Switzerland.
authors.forename: P C
authors.initials: PC
authors.lastname: Baumann
authors.forename: B J
authors.initials: BJ
authors.lastname: Meyer
authors.forename: M
authors.initials: M
authors.lastname: Maggiorini
authors.forename: H R
authors.initials: HR
authors.lastname: Ha
authors.forename: A
authors.initials: A
authors.lastname: Gallino
authors.forename: F
authors.initials: F
authors.lastname: Follath
mesh_terms: D000328:Adult; D000368:Aged; D002316:Cardiotonic Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D014882:Water-Electrolyte Balance / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D007093:Imidazoles; C039686:piroximone