Objective of the present study was to investigate the elimination kinetics of
quinaprilat and
perindoprilat, the active metabolites of
angiotensin-converting enzyme (
ACE) inhibitors quinapril and
perindopril, in hypertensive patients with
renal failure under haemodialysis to evaluate the appropriate duration of off-dose of these drugs before starting of
low-density lipoprotein (
LDL)
apheresis. The informed consent was received from 12 hypertensive patients with
renal failure, who were under haemodialysis (42 to 62 years). The patients received
oral administration of
quinapril (10 mg) or
perindopril (2 mg) once a day for four weeks. First, to evaluate the dialyzability of each metabolite, blood samples were collected before and after haemodialysis one week after the repeated doses. Second, to evaluate the elimination kinetics of
quinaprilat or
perindoprilat, blood samples were collected at 24, 72, 120, 192 and 240 h after the final administration. Plasma concentrations of
quinaprilat and
perindoprilat were measured by high-performance liquid chromatography (HPLC) and radioimmunoassay, respectively. Pharmacokinetic parameters were determined by a model-dependent method. Values of haemodialysis clearance (CL(HD)) and extraction ratio (ER) were 51.5+/-30.2 ml/min and 0.35+/-0.21 for
quinaprilat and 108.1+/-5.9 ml/min and 0.75+/-0.04 for
perindoprilat, respectively. The terminal elimination half-lives of
quinaprilat and
perindoprilat were 60.7+/-2.1 and 79.9+/-14.0 h, respectively. The dialyzability of
perindoprilat was much higher than that of
quinaprilat probably due to low protein binding potency. The present study suggests that hypertensive patients receiving chronic
therapy with
quinapril or
perindopril on haemodialysis should be withdrawn for at least 2 to 3 weeks before
LDL apheresis.