DPI 201-106 for severe congestive heart failure.
DPI 201-106 is a new oral inotropic agent that exerts its effects through a novel mechanism of action, namely, by enhancing sensitivity of myofilaments to calcium and prolonging inward sodium current. In a double-blind, randomized, placebo-controlled fashion, single oral doses (80 and 100 mg) of DPI 201-106 were administered to 15 patients with severe congestive heart failure. Dose-dependent increases in cardiac index (25%, p = 0.016), left ventricular stroke work index (24%, p = 0.018), left ventricular stroke volume index (32%,p = 0.005) and QTc interval (7%, p = 0.009) were observed. Significant effects on heart rate and systemic arterial pressure were not observed. Positive correlations of QTc interval with DPI plasma level (r = 0.64, p = 0.0001), stroke work index (r = 0.47, p = 0.0001) and ventricular ectopic activity on ambulatory electrocardiography (r = 0.49, p = 0.0001) were observed. Maximum changes occurred approximately 3 to 4 hours after ingestion and lasted more than 8 hours. Plasma drug levels were consistent with a 2-compartment model exhibiting first-order absorption and elimination kinetics. DPI 201-106 produced hemodynamic improvement in patients with severe congestive heart failure.
Kostis
J B
JB
Division of Cardiovascular Diseases and Hypertension, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903-0019.
Lacy
C R
CR
Raia
J J
JJ
Dworkin
J H
JH
Warner
R G
RG
Casazza
L A
LA
D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000097:blood / Q000627:therapeutic use*; D011897:Random Allocation
D010879:Piperazines; C046261:DPI 201-106