Clinicopharmacological studies of a newly synthesized cardiotonic agent (TA‐064) in patients with congestive heart failure

Abstract In animal experiments, a new inotropic agent, (‐)‐(R)‐1 ‐( p ‐hydroxphenyl)‐2‐[(3,4‐dimethoxyphenetyl)amino]ethanol, designated TA‐064 was found to possess a more positive inotropic than chronotropic action. Its effectiveness and lack of significant toxicity make it beneficial for clinical use as a cardiotonic in human heart failure. The effects of TA‐064 were investigated in patients with various types of heart disease (n=29). Cardiac output increased, left ventricular end‐systolic dimension decreased, and left ventricular fractional shortening increased for 15 minutes after a single intravenous dose (1 mg). The plasma level of TA‐064 at the cessation of infusion was 61.1 ± 49.6 ng/ml and thereafter declined biexponentially. After a single oral dose (10 mg), TA‐064 appeared in the plasma at 30 minutes and reached its peak levels of 13.7 ± 5.6 ng/ml at 60 minutes. Seven hours later, the plasma level was 5.9 ± 3.1 ng/ml which was considered to be within the effective range according to the results after intravenous administration. In conclusion, minimal effective plasma levels of TA‐064 are obtained by oral administration of 10 mg three times a day.