HEMODYNAMIC-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 f ailure, NYHA II-IV, requiring addition of an ACE inhibitor to their ex isting therapy were randomised to receive double-blind a single dose o f quinapril 2.5 mg p.o. or matching placebo after 24-48 h supervised d iuretic withdrawal. 2 The effect of treatment on resting supine blood pressure, heart rate, plasma angiotensin converting enzyme (ACE) and c irculating 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 pl acebo, 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 ac tivity 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 2 4 h post dose. t(max) for quinapril was seen at 2.6 +/- 1.2 h. while t (max) for quinaprilat was at 3.6, +/- 0.8 h. 4 Treatment with quinapri l 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 place bo. 5 Compared with placebo, quinapril 2.5 mg inhibits plasma ACE by o ver 60% for 24 h and reduces blood pressure for at least 10 h in patie nts with stable, chronic congestive heart failure. The blood pressure fall, although moderate and well tolerated, is more sustained than pre viously described for quinapril in heart failure.