Pharmacokinetics of Quinapril and its Active Metabolite Quinaprilat During Continuous Ambulatory Peritoneal Dialysis

Abstract

The pharmacokinetics of quinapril, a novel angiotensin converting enzyme (ACE) inhibitor, and its active metabolite, quinaprilat, were determined following a single 20-mg oral dose of quinapril in six patients with chronic renal failure maintained on continuous ambulatory peritoneal dialysis (CAPD). Overall, quinapril was well tolerated by these CAPD patients, with mild and transient side effects, not unexpected in this clinical setting, which included pruritus, headache, nausea, and cough. Blood pressure reduction was observed in four of six patients, with onset reliably two to four hours after dosing and duration up to 48 hours, associated with quinaprilat concentrations in plasma above 90 ng/mL for at least 33 hours postdose. Two patients experienced significant hypotension, systolic blood pressure below 90 mm Hg, which responded promptly to oral fluid administration and/or reduction in dialysate tonicity. The pharmacokinetic profile of quinapril in these CAPD patients was not significantly different from that previously observed in healthy subjects with normal renal function and in patients with moderate to severe renal dysfunction not yet requiring dialysis (RDND). The apparent elimination half-life of quinapril was approximately one hour, with negligible dialysate excretion. The pharmacokinetic profile of quinaprilat in these CAPD patients was similar to that previously observed in patients with RDND. The elimination half-life of quinaprilat was markedly prolonged when compared to that in healthy subjects and averaged 20 hours, with only a small amount of quinaprilat excreted in dialysate (mean = 2.6% of total dose).(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics and pharmacodynamics of quinaprilat after low dose quinapril in patients with terminal renal failure

“…In HD patients the reported half life of quinaprilat has been 17.5 (8) (SD) h [3] and 20.1 (10.1) (SD) h in CAPD patients [4]. Half lives in this study were 30 to 34.1 h in HD and CAPD patients, respectively.…”

“…The tmax reported in CAPD patients after 20 mg was 5.4 (2.5) (SD) h [4] and 4.5 (2.5) (SD) h in chronic HD patients [3]. For comparison, the tmax of captopril was about 1 h in healthy subjects, and it has been reported not to be changed (0.7-2 h) in HD [5] and CAPD (1.1 h) patients [6].…”

“…The elimination half life is prolonged in patients with impaired renal function [2]. The pharmacokinetics of quinapril and quinaprilat have previously been studied in patients on maintenance haemodialysis during a haemodialysis session [3], and during continuous peritoneal dialysis (CAPD) [4], using single doses of 20 mg p. o. The effects of even lower doses of quinapril have not been examined in HD or CAPD patients.…”