Elimination Kinetics of Quinaprilat and Perindoprilat in Hypertensive Patients with Renal Failure on Haemodialysis
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概要
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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 240h 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±30.2ml/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suggests that hypertensive patients receiving chronic therapy with quinapril or perindopril on haemodialysis should be withdrawn for at least 2 to 3 weeks before LDL apheresis.
- 公益社団法人日本薬学会の論文
- 2003-06-01
著者
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YAMADA Shigeki
Department of Neurosurgery, Kyoto University Graduate School of Medicine
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Nabeshima Toshitaka
Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, J
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Seno Hachiro
Department Of Internal Medicine. Kaikokai Nagoya Kyoritsu Ho.pital
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Kawahara Hirohisa
Department Of Internal Medicine. Kaikokai Nagoya Kyoritsu Ho.pital
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Nabeshima Toshitaka
Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Meijo University
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Muraoka Isao
Department Of Hospital Pharmacy Nagoya University School Of Medicine
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Muraoka Isao
Department Of Neuropsychopharmacologv And Hospital Pharmacy Nagoya University Graduated School Of Me
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Yamada Shigeki
Department Of Medicine Jichi Medical University Omiya Medical Center
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KATO Kana
Department of Pharmacy, Kaikokai Nagoya Kyoritsu Hospital
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HIROMI Yoko
Department of Pharmacy, Kaikokai Nagoya Kyoritsu Hospital
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TAKASU Rie
Department of Pharmacy, Kaikokai Nagoya Kyoritsu Hospital
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Hiromi Yoko
Department Of Pharmacy Kaikokai Nagoya Kyoritsu Hospital
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Takasu Rie
Department Of Pharmacy Kaikokai Nagoya Kyoritsu Hospital
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Kato Kana
Department Of Pharmacy Kaikokai Nagoya Kyoritsu Hospital
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Yamada Shigeki
名古屋共立病院
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Yamada Shigeki
Department Of Biochemistry Research Laboratory Of Applied Biochemistry Tanabe Seiyaku Co. Ltd.
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Muraoka Isao
Department of Exercise Physiology, Faculty of Sport Sciences, Waseda University
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NABESHIMA Toshitaka
Department of Neuropsychopharmacologv and Hospital Pharmacy, Nagoya University Graduated School of Medicine
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