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Clinical Pharmacology of Quinapril in Healthy Volunteers and in Patients with Hypertension and Congestive Heart Failure

Edward Posvar, M. D.

Allen J. Sedman, M. D.

Clinical Pharmacology Parke-Davis Pharmaceutical Research Division Warner-Lambert Co. 2800 Plymouth Rd. Ann Arbor, Michigan 48105

Quinapril is converted to quina prilat, a long-acting angiotensin con verting enzyme (ACE) inhibitor, and is currently being studied for the treatment of hypertension and con gestive 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 angiotension I pressor response oc curred after administration of quina pril doses of 0.625 mg to 20 mg. In addition, plasma renin activity in creased and aldosterone and an giotensin II concentrations decreased following single or multiple doses of quinapril.

Subsequently, dose-ranging stud ies 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 antihy pertensive effect. Therefore, a defini tive, multiple-dose, placebo-con trolled, double-blind study of 5, 10, and 20 mg once daily doses of quina pril was performed. Quinapril doses of 10 mg and 20 mg were statistically significantly superior to placebo (p < 0.05) in lowering sitting diastolic blood pressure (DBP), whereas 5 mg of quinapril had only marginal clini cal effectiveness. A twenty-four-hour blood pressure monitoring study in dicated that quinapril administered once or twice daily effectively low ered DBP in patients with mild to moderate hypertension. This study suggested, however, that some pa tients may not achieve sustained re ductions 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 favor able hemodynamic effects were dem onstrated after the administration of quinapril. Quinapril doses of 2.5 mg to 10 mg increased cardiac index by 30% and decreased peripheral vascu lar resistance and pulmonary capil lary wedge pressure by 20% to 30%.

Angiology, Vol. 40, No. 4 part_2, 360-369 (1989)
DOI: 10.1177/000331978904000405


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This article has been cited by other articles:

				S. C. Olson, A. M. Horvath, B. M. Michniewicz, A. J. Sedman, W. A. Colburn, P. G. Welling, and S. C. Olson The Clinical Pharmacokinetics of Quinapril Angiology, January 1, 1989; 40(4_part_2): 351 - 359. [Abstract] [PDF]

				J. S. Banas JR. Preliminary Hemodynamic Report of the Efficacy and Safety of Quinapril in Acute and Chronic Treatment of Patients with Congestive Heart Failure Angiology, January 1, 1989; 40(4_part_2): 396 - 404. [Abstract] [PDF]