Quinapril--a preclinical review of the pharmacology, pharmacokinetics, and toxicology.

Quinapril is an orally active, non-peptide, nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor that acts potently and specifically to interrupt the conversion of angiotensin I to angiotensin II in both plasma and tissue. Quinapril is enzymatically hydrolyzed to a pharmacologically active diacid form quinaprilat. Quinapril is efficacious in hypertensive models exhibiting both high (renal hypertensive rats, diuretic-treated dogs) and normal (spontaneously hypertensive rats) plasma renin activity. Quinapril does not prevent the development of hypertension when plasma renin activity (PRA) is markedly suppressed as in the deoxycorticosterone-saline treated rat. Hemodynamic studies in dogs indicate that quinapril decreases total peripheral and renal vascular resistance. Quinaprilat produces natriuresis and mild diuresis at doses that do not alter mean arterial blood pressure. Quinapril has the potential to affect plasma lipids beneficially or at least be "lipid neutral." Oral absorption of quinapril is rapid in rats, dogs, and monkeys. There is rapid and extensive distribution of radiolabel to most tissues except brain. Plasma radiolabel concentration-time profiles exhibit polyexponential decay with a prolonged terminal phase at low concentrations in all species. Metabolism to compounds other than quinaprilat is not extensive. Quinapril is excreted primarily as quinaprilat and to a lesser degree as quinapril. Quinapril is well tolerated in a variety of pharmacologic safety screens and its toxicity profile is similar to that of other ACE inhibitors. Quinapril does not adversely affect reproduction; it is not teratogenic, carcinogenic, or mutagenic.(ABSTRACT TRUNCATED AT 250 WORDS)