Elimination kinetics of quinaprilat and perindoprilat in hypertensive patients with renal failure on haemodialysis

Shigeki Yamada, Isao Muraoka, Kana Kato, Yoko Hiromi, Rie Takasu, Hachiro Seno, Hirohisa Kawahara, Toshitaka Nabeshima

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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 (CLHD) 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suggests that hypertensive patients receiving chronic therapy with quinapril or perindopril on haemodialysis should be withdrawn for at least 2 to 3 weeks before LDL apheresis.

Original languageEnglish
Pages (from-to)872-875
Number of pages4
JournalBiological and Pharmaceutical Bulletin
Volume26
Issue number6
DOIs
Publication statusPublished - 06-2003
Externally publishedYes

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perindoprilat
Renal Insufficiency
Renal Dialysis
Perindopril
Blood Component Removal
LDL Lipoproteins
Informed Consent
Angiotensin-Converting Enzyme Inhibitors
Protein Binding
Radioimmunoassay
Oral Administration
quinaprilat
Pharmacokinetics
High Pressure Liquid Chromatography

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

Yamada, Shigeki ; Muraoka, Isao ; Kato, Kana ; Hiromi, Yoko ; Takasu, Rie ; Seno, Hachiro ; Kawahara, Hirohisa ; Nabeshima, Toshitaka. / Elimination kinetics of quinaprilat and perindoprilat in hypertensive patients with renal failure on haemodialysis. In: Biological and Pharmaceutical Bulletin. 2003 ; Vol. 26, No. 6. pp. 872-875.
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Elimination kinetics of quinaprilat and perindoprilat in hypertensive patients with renal failure on haemodialysis. / Yamada, Shigeki; Muraoka, Isao; Kato, Kana; Hiromi, Yoko; Takasu, Rie; Seno, Hachiro; Kawahara, Hirohisa; Nabeshima, Toshitaka.

In: Biological and Pharmaceutical Bulletin, Vol. 26, No. 6, 06.2003, p. 872-875.

Research output: Contribution to journalArticle

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T1 - Elimination kinetics of quinaprilat and perindoprilat in hypertensive patients with renal failure on haemodialysis

AU - Yamada, Shigeki

AU - Muraoka, Isao

AU - Kato, Kana

AU - Hiromi, Yoko

AU - Takasu, Rie

AU - Seno, Hachiro

AU - Kawahara, Hirohisa

AU - Nabeshima, Toshitaka

PY - 2003/6

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N2 - 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 (CLHD) 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.

AB - 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 (CLHD) 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.

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