Pharmacokinetics of quinapril and its active metabolite quinaprilat during continuous ambulatory peritoneal dialysis.
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)
Swartz
R D
RD
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0364.
Starmann
B
B
Horvath
A M
AM
Olson
S C
SC
Posvar
E L
EL
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000009:adverse effects / Q000493:pharmacokinetics*; D007676:Kidney Failure, Chronic / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D000077583:Quinapril; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C054501:quinaprilat; D000077583:Quinapril