Hemodynamic and hormonal effects of quinaprilat in patients with congestive heart failure.
OBJECTIVE
To assess the pharmacodynamic activity and safety of rising single and multiple doses of intravenous quinaprilat compared with placebo in patients with New York Heart Association (NYHA) class III and IV congestive heart failure who were receiving digitalis or diuretic therapy or both.


METHODS
Patients were randomly assigned to three treatment groups to receive low (0.5 to 1.0 mg), medium (1.0 and 2.5 mg), or high (5.0 and 10.0 mg) single intravenous doses of quinaprilat or placebo on day 1. On the basis of responses observed on day 1, the three treatment groups received stable multiple intravenous doses of either quinaprilat or placebo every 6 hours on days 2 and 3. Hemodynamic measurements, hormonal assessments, and safety were evaluated before and at specified intervals during the study.


RESULTS
Compared with placebo, single and multiple doses of quinaprilat increased cardiac index and reduced pulmonary capillary wedge pressure, mean arterial pressure, systemic vascular resistance, and right atrial pressure in a dose-related manner. No clinically important change in heart rate was observed. Hemodynamic changes after multiple-dose quinaprilat administration were similar to those observed after single doses and were generally sustained during the 6-hour dosing interval. Relative to placebo, quinaprilat reduced plasma angiotensin converting enzyme (ACE) activity, angiotensin II concentration, and aldosterone concentration and increased plasma renin activity; no prominent changes in plasma catecholamine and atrial natriuretic peptide concentrations were observed. There were no clinically important drug-related changes in the safety parameters.


CONCLUSIONS
Single and multiple intravenous doses of 0.5 to 10 mg quinaprilat are well-tolerated and produce favorable dose-dependent hemodynamic effects and hormonal changes consistent with those expected of an ACE inhibitor in patients with NYHA class III and IV congestive heart failure.
Mitrovic
V
V
Department of Clinical Pharmacology, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105-2430, USA.
Mudra
H
H
Bonzel
T
T
Schmidt
W
W
Strand
J C
JC
Bakovic-Alt
R
R
Posvar
E L
EL
D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D007546:Isoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D012083:Renin / Q000097:blood; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000804:Angiotensin II; C054501:quinaprilat; D000450:Aldosterone; D007703:Peptidyl-Dipeptidase A; D012083:Renin