Haemodynamic response and pharmacokinetics after the first dose of quinapril in patients with congestive heart failure.
1. Twenty-four elderly patients with stable, chronic congestive heart failure, NYHA II-IV, requiring addition of an ACE inhibitor to their existing therapy were randomised to receive double-blind a single dose of quinapril 2.5 mg p.o. or matching placebo after 24-48 h supervised diuretic withdrawal. 2. The effect of treatment on resting supine blood pressure, heart rate, plasma angiotensin converting enzyme (ACE) and circulating plasma renin activity was compared between groups over the first 24 h after dosing. The pharmacokinetic profiles of quinapril and the active metabolite quinaprilat were determined. 3. Compared with placebo, quinapril caused a statistically significant but modest fall in blood pressure from 3 to 10 h post dose. The maximum fall of 12 mm Hg (95% C.I. 5.4-18.5) was seen at approximately 5 h. Circulating ACE activity was 40% inhibited within 1 h. Maximum ACE inhibition (83.6%, 95% C.I. 76.7-90.5) was observed at 3 h. ACE remained 60% inhibited at 24 h post dose. tmax for quinapril was seen at 2.6 +/- 1.2 h. while tmax for quinaprilat was at 3.6, +/- 0.8 h. 4. Treatment with quinapril was associated with a significant rise in plasma renin activity (PRA) of 8.83 ng AI ml-1 h-1 (95% C.I. 0.30-17.96) compared with placebo. 5. Compared with placebo, quinapril 2.5 mg inhibits plasma ACE by over 60% for 24 h and reduces blood pressure for at least 10 h in patients with stable, chronic congestive heart failure. The blood pressure fall, although moderate and well tolerated, is more sustained than previously described for quinapril in heart failure.
Squire
I B
IB
University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow.
Macfadyen
R J
RJ
Lees
K R
KR
Hillis
W S
WS
Reid
J L
JL
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D004232:Diuretics / Q000008:administration & dosage / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D000077583:Quinapril; D012083:Renin / Q000097:blood; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D000077583:Quinapril