Clinicopharmacological studies of a newly synthesized cardiotonic agent (TA-064) in patients with congestive heart failure.
In animal experiments, a new inotropic agent, (-)-(R)-1-(p-hydroxyphenyl)-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.
Bito
K
K
First Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan.
Kinoshita
M
M
Mashiro
I
I
Ozaki
N
N
Sakoda
S
S
Tsutamoto
T
T
Motomura
M
M
Mitsunami
K
K
Fukuhara
T
T
Kawakita
S
S
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D004452:Echocardiography; D004983:Ethanolamines / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged
D002316:Cardiotonic Agents; D004983:Ethanolamines; C037293:denopamine