PMID- 8681494
OWN - NLM
STAT- MEDLINE
DCOM- 19960821
LR  - 20140109
IS  - 0009-9236 (Print)
IS  - 0009-9236 (Linking)
VI  - 59
IP  - 6
DP  - 1996 Jun
TI  - Hemodynamic and hormonal effects of quinaprilat in patients with congestive heart 
      failure.
PG  - 686-98
AB  - 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.
FAU - Mitrovic, V
AU  - Mitrovic V
AD  - Department of Clinical Pharmacology, Parke-Davis Pharmaceutical Research, 
      Division of Warner-Lambert Company, Ann Arbor, MI 48105-2430, USA.
FAU - Mudra, H
AU  - Mudra H
FAU - Bonzel, T
AU  - Bonzel T
FAU - Schmidt, W
AU  - Schmidt W
FAU - Strand, J C
AU  - Strand JC
FAU - Bakovic-Alt, R
AU  - Bakovic-Alt R
FAU - Posvar, E L
AU  - Posvar EL
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Isoquinolines)
RN  - 0 (Tetrahydroisoquinolines)
RN  - 11128-99-7 (Angiotensin II)
RN  - 34SSX5LDE5 (quinaprilat)
RN  - 4964P6T9RB (Aldosterone)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
RN  - EC 3.4.23.15 (Renin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aldosterone/blood
MH  - Angiotensin II/blood
MH  - Angiotensin-Converting Enzyme Inhibitors/adverse effects/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Heart Failure/*drug therapy/physiopathology
MH  - Hemodynamics/*drug effects
MH  - Humans
MH  - Injections, Intravenous
MH  - Isoquinolines/adverse effects/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Peptidyl-Dipeptidase A/blood
MH  - Renin/blood
MH  - *Tetrahydroisoquinolines
EDAT- 1996/06/01 00:00
MHDA- 1996/06/01 00:01
CRDT- 1996/06/01 00:00
PHST- 1996/06/01 00:00 [pubmed]
PHST- 1996/06/01 00:01 [medline]
PHST- 1996/06/01 00:00 [entrez]
AID - S0009-9236(96)90009-0 [pii]
AID - 10.1016/S0009-9236(96)90009-0 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 1996 Jun;59(6):686-98. doi: 10.1016/S0009-9236(96)90009-0.