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: P C Baumann, B J Meyer, M Maggiorini, H R Ha, A Gallino, F Follath
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 21 Issue 3 Pg. 489-95 (Mar 1993) ISSN: 0160-2446 [Print] United States
• PMID: 7681513 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Imidazoles
• piroximone

Topics

• Adult
• Aged
• Cardiotonic Agents (pharmacokinetics, pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Heart Failure (drug therapy)
• Hemodynamics (drug effects)
• Humans
• Imidazoles (pharmacokinetics, pharmacology, therapeutic use)
• Infusions, Intravenous
• Male
• Middle Aged
• Water-Electrolyte Balance (drug effects)