The pharmacokinetics and pharmacodynamics of quinapril and quinaprilat in renal impairment.

Abstract

1. The pharmacokinetics and pharmacodynamics of quinapril and its active metabolite quinaprilat were studied in 20 subjects with renal function varying from normal to severe renal failure, during the approach to and at steady‐state, and for 72 h after cessation of quinapril 20 mg orally for 7 days. 2. The apparent oral plasma clearance of quinaprilat (dose of quinapril equivalent/AUC of quinaprilat) was directly related to creatinine clearance (CLCr). The predicted apparent oral clearance of quinaprilat was zero when CLCr was zero, suggesting minimal extrarenal elimination. 3. Peak and trough concentrations of quinaprilat, and its apparent elimination half‐life, varied inversely with CLCr. 4. Trough concentrations of quinaprilat showed no accumulation between 2 and 7 days, even in severe renal impairment. 5. There was a weak relationship between the oral plasma clearance of quinapril and CLCr. 6. ACE inhibition was marked and prolonged in all subjects, with 50% inhibition at 2.7 +/− 1.9% ng ml‐1 of quinaprilat. The time for which ACE inhibition was greater than 90% was related inversely to CLCr. 7. Aldosterone concentrations and plasma renin activity responded in a predictable way, but with no clear relationship To CLCr. 8. Atrial natriuretic peptide concentrations were not affected by quinapril administration. 9. Glomerular filtration rate, as measured by Tc99mDTPA clearance, was not affected by quinapril administration. 10. Blood pressure at steady‐state decreased significantly in the subjects with hypertension. The changes in blood pressure were not related to renal function. 11. These results suggest that the dosage rate of quinapril may have to be altered in renal impairment.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of Quinapril in Children: Assessment during Substitution for Chronic Angiotensin‐Converting Enzyme Inhibitor Treatment

“…The intercept of the relationship was not significantly different from 0 ( p = 0.21), indicating that the nonrenal elimination component of quinaprilat is negligible in pediatric patients. The intercept was set to 0 in the regression analysis; the observed correlation ( r 2 = 0.908, slope = 0.999, p < 0.001) between quinaprilat CL/F and CL cr indicates that CL cr is a good predictor of quinaprilat oral clearance in pediatric patients just as it is in adults 12 , 13 …”

The pharmacokinetics of quinapril and quinaprilat in patients with congestive heart failure.

“…Quinapril and quinaprilat in plasma were assayed using gas chromatography/electron capture. Details of the method and its precision have been given previously [1].…”

“…Quinapril is a nonsulphydryl angiotensin converting enzyme (ACE) inhibitor which is de-esterified in vivo to the active di-acid metabolite quinaprilat. Quinaprilat is largely excreted unchanged by the kidneys and its clearance is directly related to renal function [1]. Quinapril, like other ACE inhibitors, is useful in the treatment of CHF.…”

“…Quinaprilat is largely excreted unchanged by the kidneys and its clearance is directly related to renal function [1]. Quinapril, like other ACE inhibitors, is useful in the treatment of CHF.…”

Effects of Chungsinoryungsan, a polyherbal complex, on the pharmacokinetic profiles of perindopril in rats

“…However, there are numerous clinical factors that alter perindopril pharmacokinetics. Since the active metabolites of perindopril are hydrolyzed in the liver and primarily excreted into the urine, the elimination kinetics can be altered in hepatic impairment (26,29), renal failure (30) or chronic heart failure (31). Ageing is also associated with the alteration in enhanced conversion to perindoprilat and the reduced renal clearance (32).…”