Pharmacokinetics and pharmacodynamics of quinaprilat after low dose quinapril in patients with terminal renal failure.
The pharmacokinetics and pharmacodynamics of the ACE inhibitor quinaprilat have been studied in six chronic haemodialysis (HD) patients and in six patients undergoing continuous ambulatory peritoneal dialysis (CAPD) after a single oral dose of 2.5 mg quinapril. Mean tmax and Cmax values (SEM) for quinaprilat in interdialytic HD patients were 4.0 (0) h and 84 (8.4) ng.ml-1 respectively, and they did not differ significantly from those in CAPD patients (4.7 (0.7) h and 64 (5.7) ng.ml-1). Elimination half lives were 30 (10.1) h (HD) and 34 (7.3) h (CAPD). Cmax, tmax, t1/2, and AUC were increased and CL was decreased compared to data reported previously after giving 2.5 mg to healthy subjects. Peritoneal clearance was calculated as 0.1 (0.1) ml.min-1, thus less than 0.5% of the dose were removed within 24 h by CAPD. ACE activity was suppressed by more than 93% between 4 and 24 h postdose (P < 0.001). It decreased in both groups with increasing plasma quinaprilat levels. Angiotensin II concentration compared to baseline was significantly decreased at 4 hours (-30.4 +/- 10%) and 24 h (-30 +/- 9.9%) (P < 0.05, n = 11), while active plasma renin concentration was still significantly increased at 48 h postdose (+ 60.2 +/- 14.5%, P < 0.01). Mean arterial pressure 24 h postdose was significantly (P < 0.05) decreased in HD (-12 mmHg) and CAPD patients (-20 mm Hg). Only two patients reported unwanted effects (fatigue, dizziness, nausea, and weakness). In conclusion, due to its long lasting effect on ACE activity and on blood pressure in terminal renal failure a starting dose of quinapril 2.5 mg o.d. may be used in hypertensive HD and CAPD patients.
Department of Internal Medicine, University Hospital Essen, Germany.
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K
Wolter
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Fritschka
D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010531:Peritoneal Dialysis, Continuous Ambulatory; D000077583:Quinapril; D006435:Renal Dialysis; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000804:Angiotensin II; C054501:quinaprilat; D007703:Peptidyl-Dipeptidase A; D000077583:Quinapril