Quinapril: A New Second-Generation Ace Inhibitor

Abstract

Quinapril is a new non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor. The drug undergoes hepatic hydrolysis into its major active diacid metabolite, quinaprilat, and two minor inactive metabolites. On a weight basis quinaprilat is three times as potent an ACE inhibitor as quinapril. Approximately 60 percent of an oral dose of quinapril is absorbed. In contrast with captopril, the absorption of quinapril is unaffected by food. Peak serum concentrations of quinapril and quinaprilat are achieved within one and two hours, respectively. Approximately 61 percent of an orally administered dose is excreted in the urine, principally as quinaprilat. The elimination half-life of quinaprilat is three hours, but is prolonged up to 11 hours in patients with renal dysfunction. Quinapril dose reduction is recommended in patients with a creatinine clearance of 0.50 mL/sec or less. In the elderly the elimination of quinaprilat is reduced and correlates well with renal function. In patients with cirrhosis the hydrolysis of quinapril to quinaprilat is impaired resulting in lower plasma quinaprilat concentrations and up to a two-fold increase in quinapril half-life. Quinaprilat has a strong binding capacity to tissue ACE allowing for once-daily dosing. The recommended starting dose for quinapril is 20 mg/d. The nature and incidence of adverse reactions to quinapril are similar to those of enalapril and captopril. Quinapril's antihypertensive efficacy is equal to that of captopril and enalapril. A small number of patients with congestive heart failure (CHF) have been treated with quinapril. Preliminary data indicate that quinapril is an equally effective therapeutic alternative to presently available ACE inhibitors in the treatment of CHF. Quinapril, a second-generation ACE inhibitor, has not been shown to offer significant clinical advantage over enalapril. In formulary evaluations quinapril may be considered therapeutically equivalent to enalapril.