Clinical pharmacology of quinapril in healthy volunteers and in patients with hypertension and congestive heart failure.
Quinapril is converted to quinaprilat, a long-acting angiotensin converting enzyme (ACE) inhibitor, and is currently being studied for the treatment of hypertension and congestive heart failure. In studies of healthy volunteers, single quinapril doses of 0.625 mg to 80 mg inhibited plasma ACE activity for up to forty-eight hours. Dose-related inhibition of angiotensin I pressor response occurred after administration of quinapril doses of 0.625 mg to 20 mg. In addition, plasma renin activity increased and aldosterone and angiotensin II concentrations decreased following single or multiple doses of quinapril. Subsequently, dose-ranging studies were conducted in patients with mild to moderate hypertension and congestive heart failure. Pilot studies suggested that 5 mg of quinapril given once daily had minimal antihypertensive effect. Therefore, a definitive, multiple-dose, placebo-controlled, double-blind study of 5, 10, and 20 mg once daily doses of quinapril was performed. Quinapril doses of 10 mg and 20 mg were statistically significantly superior to placebo (p less than 0.05) in lowering sitting diastolic blood pressure (DBP), whereas 5 mg of quinapril had only marginal clinical effectiveness. A twenty-four-hour blood pressure monitoring study indicated that quinapril administered once or twice daily effectively lowered DBP in patients with mild to moderate hypertension. This study suggested, however, that some patients may not achieve sustained reductions in DBP over the entire twenty-four-hour interval with quinapril administered once daily and may require twice daily therapy. In studies of patients with refractory congestive heart failure, acute favorable hemodynamic effects were demonstrated after the administration of quinapril.(ABSTRACT TRUNCATED AT 250 WORDS)
Sedman
A J
AJ
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan.
Posvar
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000803:Angiotensin I / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; 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; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007546:Isoquinolines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D000077583:Quinapril; D011897:Random Allocation; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D000077583:Quinapril