Hemodynamic effects of a new type III phosphodiesterase inhibitor (CI-914) for congestive heart failure.
Hemodynamic response after intravenous and oral administration of a new phosphodiesterase inhibitor, CI-914, was studied in 13 patients with severe congestive heart failure. Comparable significant increases in cardiac index of 26% (p less than 0.01) and 19% (p less than 0.02) after intravenous and oral administration were observed. Systemic vascular resistance, right atrial and pulmonary artery wedge pressure decreased significantly after intravenous drug administration. Although similar changes occurred after oral administration, they were not statistically significant. Peak CI-914 plasma concentration occurred 2.3 +/- 2.2 hours after oral drug administration and exhibited measurable hemodynamic effects for up to 10 to 12 hours. Seven of the 13 patients received long-term oral CI-914 for as long as 12 weeks and exhibited an improvement in New York Heart Association functional class and exercise capacity. Five patients died with progressive heart failure, 1 patient died suddenly and 1 died of sepsis. The drug was well tolerated and appears to have potential as a cardiotonic agent.
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011724:Pyridazines / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; C042527:imazodan