PHARMACOKINETICS AND PHARMACODYNAMICS OF QUINAPRILAT IN HYPERTENSIVE DIALYSIS PATIENTS

The pharmacokinetics and pharmacodynamics of quinaprilat were examined in hypertensive dialysis patients. After a single low dose (2.5 mg p. o.) of the ACE inhibitor quinapril in 6 chronic haemodialysis patient s and in 6 patients undergoing continuous ambulatory peritoneal dialys is (CAPD) the pharmacokinetics were altered compared to healthy subjec ts. The mean (+/- SEM) resulting elimination half-lives (t1/2) were 30 +/- 10.1 (HD) and 34.1 +/- 7.3 h (CAPD) compared to 2.1 h in healthy volunteers. The total body clearance (CL) was 11.8 +/- 4.9 ml/min (HD) and 11.9 +/- 4 ml/min (CAPD) and lower than the 220 ml/min reported i n healthy subjects. Only 0.5% of the dose were eliminated by CAPD duri ng 48 h, i. e. a mean peritoneal clearance of 0.1 +/- 0.1 ml/min. The ACE activity was suppressed significantly in all patients up to 48 h ( p <0.005), the angiotensin II plasma concentration was significantly d ecreased 24 h after drug intake (p <0.05) and the active renin concent ration in plasma was increased up to 48 h (p <0.05). The mean arterial blood pressure (MAP) was lowered up to 24 h after 2.5 mg quinapril (p <0.05). An initial dose of 2.5 mg of quinapril may be therefore admin istered initially in hypertensive dialysis patients when indicated.