Interindividual Variability in 5-Fluorouracil Metabolism and Procainamide N-Acetylation in Human Liver Cytosol(Biochemistry/Molecular Biology)
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概要
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We investigated the enzymatic kinetics and interindividual variability of the metabolism of 5-fluorouracil and procainamide by human liver cytosol and/or microsomes. The K_m values for the 5-fluorouracil dihydropy-rimidine dehydrogenase (DPD) and procainamide N-acetyltransferase activities in pooled liver cytosol, and procainamide hydrolysis in pooled liver microsomes were 3.9, 1670, and 969μM, respectively, and the intrinsic clearance (V_<max>/K_m) values for these reactions were 128, 0.192, and 0.0059μl/min/mg protein, respectively. The cytosolic activities of 5-fluorouracil metabolism and procainamide N-acetylation ranged from 145 to 790 (469±156, mean±S.D., n=22) and <1 to 152 (52±48, n=12) pmol/min/mg protein, respectively, and the DPD activity of 5-fluorouracil was neither gender-related nor age-dependent. Procainamide N-acetylation activities among 12 human cytosol samples were highly correlated with sulfamethazine N-acetylation activities, suggesting that procainamide N-acetylation is catalyzed by N-acetyltransferase-2. These results suggest that the N-acetylation reaction is more important than the hydrolysis in the metabolic pathway of procainamide, and that there are large interindividual differences in the enzyme activities towards the respective metabolic pathways of 5-fluorouracil and procainamide in human liver.
- 公益社団法人日本薬学会の論文
- 2005-06-01
著者
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OHNO Yasuo
Division of Pharmacology, National Institute of Health Science
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Kawamura A
Pharmacokinetic Research Laboratories Fujisawa Pharmaceutical Co. Ltd.:(present Address)analysis And
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Shirage Toshifumi
Departmnet Of Pharmacolinetics And Drug Metabolism Pharma Ceutical And Pharmacolinetic Research Labo
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Shiraga T
Biopharmaceutical And Pharmacokinetic Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Niwa T
近畿大学 薬学部
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Ohno Yasuo
国立医薬品食品衛生研究所
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NIWA Toshiro
Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
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SHIRAGA Toshifumi
Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
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KAGAYAMA Akira
Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
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Niwa T
Post-marketing Development Research Center Fujisawa Pharmaceutical Co. Ltd.
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Kagayama Akira
Biopharmaceutical And Pharmacokinetic Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Shiraga Toshifumi
Biopharmaceutical And Pharmacokinetic Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Ohno Yasuo
Division Of Internal Medicine And Thoracic Oncology National Cancer Center Hospital
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Niwa Toshiro
Post Marketing Product Development Astellas Pharma Inc.
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Kawamura Akio
Department Of Surgery Sapporo Hokuyu Hospital Research Institute For Artificial Organs Transplantati
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