Overview of the clinical development of quinapril.
Quinapril hydrochloride is the newest member of a family of angiotensin-converting enzyme (ACE) inhibitors. On completion of laboratory and animal studies, a clinical program was initiated to evaluate the antihypertensive and other properties of the drug in human subjects. The initial phase of clinical development was concerned with the pharmacokinetics and pharmacology of quinapril. The latter studies established a dose range for the drug and explored its effect on human hemodynamics and blood pressure. Safety and interactions with other drugs were also examined. Subsequent studies explored the safety and efficacy of quinapril in patients with mild to moderate hypertension and, later, in patients with more severe hypertension. Results of these studies supported the recommendation of a once daily dosage of quinapril, 10-40 mg, as first-line therapy in the management of hypertension, with diuretics as concomitant therapy as required in patients with severe hypertension. Quinapril has also been found to be the most potent of all available ACE inhibitors in binding to tissue ACE, which may contribute to its potent and sustained duration of action. Clinical evaluation of quinapril has also been undertaken in patients with congestive heart failure. Initial findings indicate that doses of 10-20 mg/day, given twice daily, are therapeutic when administered with diuretic or digitalis. Safety of the drug has been established in 2700 patients.
Frank
G J
GJ
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004341:Drug Evaluation; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007546:Isoquinolines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D000077583:Quinapril; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000077583:Quinapril