Hemodynamic, hormonal, and pharmacokinetic aspects of treatment with lisinopril in congestive heart failure.
The acute hemodynamic, hormonal, and pharmacokinetic aspects of treatment with the angiotensin-converting enzyme (ACE) inhibitor lisinopril were assessed in two studies in 24 patients with chronic stable congestive heart failure (CHF). Lisinopril, the lysine analogue of enalaprilat, is biologically active following absorption and is cleared via the urine without any known metabolic transformation. In the hemodynamic study, single doses of lisinopril (1.25-10.0 mg) were administered on days 1 and 3, each followed by 48 h of intensive hemodynamic observation in 12 patients. Arterial and mixed venous blood from the right atrium were sampled frequently and assayed for angiotensin I, angiotensin II, ACE activity, plasma renin activity, renin substrate, plasma aldosterone, and serum drug concentration. Across all doses, reductions in mean arterial pressure (-17.2%), mean pulmonary capillary wedge pressure (-28.0%), and systemic vascular resistance (-25.6%) were observed compared to baseline values. No significant changes in heart rate or cardiac index were observed. The analysis of the hormonal parameters indicate potent inhibition of the renin-angiotensin-aldosterone system for a period exceeding 24 h. In the pharmacokinetic study, 12 hospitalized patients with chronic CHF received lisinopril both orally and intravenously, with each dose followed by a 72-h arterial blood and urine sampling schedule. Arterial blood pressure was monitored continuously for 6 h following each dosage using an intraarterial cannula. Mean urinary recovery of lisinopril was found to be 15% following oral administration and 88% following intravenous administration. Maximal serum drug concentration occurred at 6 h after oral drug.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D006728:Hormones / Q000097:blood*; D006801:Humans; D007700:Kinetics; D017706:Lisinopril; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011897:Random Allocation; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D006728:Hormones; D000804:Angiotensin II; D000450:Aldosterone; D004656:Enalapril; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A; D012083:Renin