Following systemic absorption,
quinapril is converted by de-esterification to
quinaprilat (the active diacid metabolite), an inhibitor of
angiotensin converting enzyme (ACE). Pharmacodynamic studies in animals indicate inhibition of ACE both in plasma and at tissue sites, such as the arterial wall and heart, following administration of
quinapril. Tissue ACE inhibition may be an important component of the mechanism of action of
quinapril (and other
ACE inhibitors) in achieving favourable effects in cardiovascular disorders.
Quinaprilat has a short elimination half-life (approximately 2 hours), but binds potently to and dissociates slowly from ACE, thus allowing once or twice daily administration of
quinapril in the treatment of patients with
hypertension or
congestive heart failure.
Quinapril 10 to 40 mg/day has achieved adequate control of blood pressure in most patients with
essential hypertension in clinical trials. Some patients required
quinapril dosages up to 80 mg/day and/or concomitant
diuretic therapy. Titrating
quinapril dosages from 10 to 40 mg/day increased response rates without increasing the incidence or severity of adverse events. Addition of
hydrochlorothiazide to
quinapril therapy improved response rates by approximately 10 to 20% in patients with
hypertension. In general, blood pressure control with
quinapril monotherapy was similar to that achieved with
enalapril or other standard
antihypertensive agents in comparative trials.
Quinapril < or = 40 mg/day improved exercise tolerance, reduced the severity and frequency of symptoms, and improved functional (New York Heart Association) class in most clinical studies of patients with
congestive heart failure. In addition, beneficial haemodynamic and echocardiographic changes achieved with
quinapril were maintained for up to 1 year with continued administration to such patients, but its effect on survival in patients with
congestive heart failure has not been reported. The tolerability profile of
quinapril is broadly similar to that of other
ACE inhibitors; pooled data from clinical trials indicated that 12% of patients with
hypertension or
congestive heart failure receiving
quinapril experienced a treatment-related adverse effects compared with 15% of
enalapril recipients and 16% of
captopril recipients. Thus,
quinapril has clearly established a role as an effective and well tolerated alternative to other
ACE inhibitors for the treatment of
hypertension and
congestive heart failure. While effects of
quinapril on survival of patients with
congestive heart failure have not been determined, large intervention studies have demonstrated improved mortality rates with other
ACE inhibitors. Further studies, including a large ongoing trial of normotensive patients with
coronary artery disease but normal left ventricular function, may also establish a role for
quinapril in treating patients with ischaemic
heart disease.