Acute hemodynamic effects of a new inotropic agent, OPC-8212, on severe congestive heart failure

The hemodynamic and clinical effects of OPC-8212, a newly synthesized, orally effective inotropic agent, were assessed for the first time in ten patients with severe congestive heart failure by means of right heart catheterization with a Swan-Ganz catheter. Cardiac output was determined by the thermodilution technique. Patients received a single oral dose of 6 mg/kg. To determine the magnitude and time-course of the effects of OPC-8212, measurements were made during an observation period before and 2, 4, 8, and 12 h after administration. Blood was also taken at these times for measurement of the concentration of plasma OPC-8212. No large meals were allowed during the first 4 h. After the single oral dose of OPC-8212, plasma concentrations increased rapidly, reaching an effective level after 8 h and peaking at 12 h. Hemodynamic performance improved as the mean OPC-8212 plasma level increased, with the maximum effect being observed between 8 and 12 h after acute administration of the drug. At 8 h, the cardiac index was increased from the baseline value of 2.4 +/- 0.2 (SEM) to 2.8 +/- 0.3 1/min/m2 (P less than 0.01). The stroke work index rose from 26.2 +/- 5.1 to 31.7 +/- 60 g . m/m2. The excessive pulmonary artery diastolic pressure fell from 22 +/- 2 to 17 +/- 3 mmHg at 8 h (P less than 0.001) and to 16 +/- 2 mmHg (P less than 0.001) at 12 h. The incidence of ventricular premature beats was not increased and no other side effects were observed.(ABSTRACT TRUNCATED AT 250 WORDS)