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Pharmacokinetics of Quinapril and Its Active Metabolite, Quinaprilat, in Patients on Chronic Hemodialysis
Author(s) -
Blum Robert A.,
Olson Stephen C.,
Kohli Romesh K.,
Horvath Ann Marie,
Sedman Allen J.,
Posvar Edward L.
Publication year - 1990
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1990.tb03574.x
Subject(s) - quinapril , hemodialysis , pharmacokinetics , medicine , active metabolite , metabolite , urology , pharmacology , ace inhibitor , angiotensin converting enzyme , blood pressure
The pharmacokinetics of quinapril and its active metabolite, quinaprilat, were evaluated in 12 patients with end‐stage renal disease (ESRD) on chronic hemodialysis. Each subject received a single 20‐mg oral dose of quinapril 4 hours before a 4‐hour hemodialysis treatment. Serial dialysate and blood samples were obtained over 4 and 96 hours, respectively. Samples were analyzed for quinapril and quinaprilat concentrations by gas chromatography. Mean t max and C max values for quinapril were 1.2 hours and 129 ng/mL, respectively. Only one patient had detectable quinapril dialysate concentrations which accounted for 2.8% of the quinapril dose. Mean apparent plasma clearance for quinapril was 1275 mL/min with a mean half‐life of 1.7 hours. Quinapril was extensively de‐esterified to its diacid metabolite, quinaprilat. Mean t max and C max for quinaprilat were 4.5 hours and 671 ng/mL, respectively. Mean apparent plasma clearance for quinaprilat was 24.0 mL/min with a mean half‐life of 17.5 hours. As with quinapril, quinaprilat was not readily dialyzable. Only 5.4% of the administered quinapril dose was recovered as quinaprilat during a single hemodialysis treatment. In view of these results, supplemental quinapril doses need not be routinely given to patients following hemodialysis. Overall, quinapril and quinaprilat pharmacokinetics in patients with ESRD on chronic hemodialysis were not markedly different from those previously observed in patients with moderate to severe renal dysfunction (CLcr < 29 mL/min) not yet requiring hemodialysis (RDND).