Oral OPC-8212 for the treatment of congestive heart failure: hemodynamic improvement and increased exercise capacity.
The chronic effects of the oral administration of OPC-8212 (3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinon e) on resting hemodynamics and exercise capacity were assessed in 15 patients with congestive heart failure (NYHA II-IV). Doses of 30 or 60 mg per day were given per os over 3.0 weeks on average (range 2-6 weeks). Multigated radionuclide ventriculography and multistage exercise testing were performed before and during OPC-8212 therapy to assess the changes in left ventricular volume and exercise capacity respectively. Systolic blood pressure showed a slight increase (from 123 +/- 3 to 129 +/- 4 mmHg) during OPC-8212 therapy, while heart rate was unchanged (69 +/- 3 vs 67 +/- 3 beats/min). The left ventricular end-diastolic volume index decreased from 127 +/- 9 to 107 +/- 7 ml/m2, and ejection fraction and the P/V index (the ratio of peak systolic pressure to left ventricular end-systolic volume index) increased during OPC-8212 therapy (from 27% +/- 3% to 30% +/- 4% and from 1.5 +/- 0.2 to 2.0 +/- 0.3 mmHg/ml/m2 respectively). NYHA functional class was improved in 9 of 15 patients, and the average peak work load achieved during exercise testing increased from 27 +/- 6 to 47 +/- 7 W. No significant adverse effect was observed in any patient. These results indicate that OPC-8212 enhances the inotropic state and, hence, reduces heart size with no change in heart rate. Moreover, it increases exercise capacity. Thus, OPC-8212 is an inotropic agent with promise for application in the long-term treatment of congestive heart failure.
D000284:Administration, Oral; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D005082:Physical Exertion; D011719:Pyrazines; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D013318:Stroke Volume / Q000187:drug effects
D002316:Cardiotonic Agents; D011719:Pyrazines; D011804:Quinolines; C041667:vesnarinone