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)