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Metabolic capabilities of cytochrome P450 enzymes in Chinese liver microsomes compared with those in Caucasian liver microsomes

文献类型：期刊论文

作者Yang, Junling1; He, Minxia M.3; Niu, Wei; Wrighton, Steven A.3; Li, Li; Liu, Yang; Li, Chuan1,2
刊名BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
出版日期2012-02
卷号73期号:2页码:268-284
关键词cytochrome P450 ethnic difference human liver microsomes
ISSN号0306-5251
DOI10.1111/j.1365-2125.2011.04076.x
文献子类Article
英文摘要AIM The most common causes of variability in drug response include differences in drug metabolism, especially when the hepatic cytochrome P450 (CYP) enzymes are involved. The current study was conducted to assess the differences in CYP activities in human liver microsomes (HLM) of Chinese or Caucasian origin. METHODS The metabolic capabilities of CYP enzymes in 30 Chinese liver microsomal samples were compared with those of 30 Caucasian samples utilizing enzyme kinetics. Phenacetin O-deethylation, coumarin 7-hydroxylation, bupropion hydroxylation, amodiaquine N-desethylation, diclofenac 4'-hydroxylation (S)-mephenytoin 4'-hydroxylation, dextromethorphan O-demethylation, chlorzoxazone 6-hydroxylation and midazolam 1'-hydroxylation/ testosterone 6 beta-hydroxylation were used as probes for activities of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A, respectively. Mann-Whitney U test was used to assess the differences. RESULTS The samples of the two ethnic groups were not significantly different in cytochrome-beta 5 concentrations but were significantly different in total CYP concentrations and NADPH-P450 reductase activity (P < 0.05). Significant ethnic differences in intrinsic clearance were observed for CYP1A2, CYP2C9, CYP2C19 and CYP2E1; the median values of the Chinese group were 54, 58, 26, and 35% of the corresponding values of the Caucasian group, respectively. These differences were associated with differences in Michaelis constant or maximum velocity. Despite negligible difference in intrinsic clearance, the Michaelis constant of CYP2B6 appeared to have a significant ethnic difference. No ethnic difference was observed for CYP2A6, CYP2C8, CYP2D6 and CYP3A. CONCLUSIONS These data extend our knowledge on the ethnic differences in CYP enzymes and will have implications for drug discovery and drug therapy for patients from different ethnic origins.
WOS关键词CONSTITUTIVE ANDROSTANE RECEPTOR ; GENETIC POLYMORPHISMS ; CLINICAL-IMPLICATIONS ; CYP1A2 ACTIVITY ; ALLELE FREQUENCIES ; DRUG-INTERACTIONS ; IN-VIVO ; JAPANESE ; VARIABILITY ; POPULATIONS
资助项目National Science and Technology Major Project of China[2009ZX09304-002] ; National Science Fund of China[30925044] ; Shanghai Science and Technology Major Project[08DZ1980200] ; Chinese Academy of Sciences[KSCX2-YW-R-191] ; Eli Lilly and Company[00000000]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000298876300014
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/278208]  
专题上海药物代谢研究中心
科研与新药推进处
通讯作者Li, Chuan
作者单位1.Chinese Acad Sci, Grad Sch, Shanghai 201203, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Lab DMPK Res Herbal Med, Shanghai 201203, Peoples R China;
3.Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA
推荐引用方式
GB/T 7714		 Yang, Junling,He, Minxia M.,Niu, Wei,et al. Metabolic capabilities of cytochrome P450 enzymes in Chinese liver microsomes compared with those in Caucasian liver microsomes[J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY,2012,73(2):268-284.
APA Yang, Junling.,He, Minxia M..,Niu, Wei.,Wrighton, Steven A..,Li, Li.,...&Li, Chuan.(2012).Metabolic capabilities of cytochrome P450 enzymes in Chinese liver microsomes compared with those in Caucasian liver microsomes.BRITISH JOURNAL OF CLINICAL PHARMACOLOGY,73(2),268-284.
MLA Yang, Junling,et al."Metabolic capabilities of cytochrome P450 enzymes in Chinese liver microsomes compared with those in Caucasian liver microsomes".BRITISH JOURNAL OF CLINICAL PHARMACOLOGY 73.2(2012):268-284.

入库方式： OAI收割

来源：上海药物研究所

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