Hemodynamic, pharmacokinetic and clinical response to CI-930 in congestive heart failure due to ischemic or dilated cardiomyopathy.
CI-930, a new type III phosphodiesterase inhibitor, was evaluated for treatment of refractory congestive heart failure. The hemodynamic, pharmacokinetic and clinical response to the drug was determined in 10 patients. At the peak plasma concentration after intravenous CI-930, cardiac index increased from 2.0 to 2.7 liters/min/m2 (p less than 0.002), pulmonary artery wedge pressure decreased from 26 to 17 mm Hg (p less than 0.001) and systemic vascular resistance decreased from 1,999 to 1,471 dynes cm-5 (p less than 0.05). Heart rate and blood pressure did not change significantly. Similar changes were observed with oral CI-930. Peak CI-930 plasma concentration occurred 1.2 +/- 0.8 hours after oral administration. Beneficial hemodynamic effects were sustained 12 to 18 hours after the oral dose. The sustained hemodynamic effects observed after oral administration appear to be related to an active metabolite of CI-930 that has prolonged duration of action and slow washout. The drug was well tolerated and has potential for treatment of congestive heart failure.
D000284:Administration, Oral; D000368:Aged; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000150:complications*; D006224:Cricetinae; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011724:Pyridazines / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D013997:Time Factors
D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; C042528:4,5-dihydro-6-(4-(imidazol-1-yl)phenyl)-5-methyl-3(2H)-pyridazinone