题名 | The role of CYP2C9 genetic polymorphism in carvedilol O-desmethylation in vitro |
作者 | |
发表日期 | 2016-02 |
发表期刊 | EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS 影响因子和分区 |
语种 | 英语 |
原始文献类型 | Article |
关键词 | Carvedilol O-desmethylation CYP2C9 CYP2D6 Enzymatic activity Genetic polymorphism Metabolism |
其他关键词 | FUNCTIONAL-CHARACTERIZATION ; CHINESE POPULATION ; METABOLISM ; PHARMACOKINETICS ; VARIANTS ; CYTOCHROME-P450 ; IDENTIFICATION ; LOSARTAN |
摘要 | We aimed at investigating the role of CYP2C9 in carvedilol O-desmethylation and identifying the effect of 35 CYP2C9 allelic variants we found in Chinese Han population on the in vitro metabolism of carvedilol. Recombinant CYP2C9 and CYP2D6 microsomes of the wild type were used to test and verify the enzymes involved in carvedilol O-desmethylation. Recombinant CYP2C9 microsomes of distinguished genotypes were used to characterize the corresponding enzyme activity toward carvedilol. 2-100 mu M carvedilol was incubated for 30 min at 37 A degrees C. The products were detected using high-performance liquid chromatography. CYP2C9 plays a certain role in carvedilol metabolism. Compared with wild-type CYP2C9*1, the intrinsic clearance (V (max)/K (m)) values of all variants toward carvedilol O-desmethylation were significantly altered. The variants exhibited significantly decreased values (from 30 to 99.8 %) due to increased K (m) and/or decreased V (max) values. We conclude that recombinant system could be used to investigate the enzymes involved in drug metabolism and these findings complement the database where CYP2C9 polymorphism interacts with biotransformation of exogenous substances like drugs and toxins. |
资助项目 | Ministry of Health of the People's Republic of China [201302008]; National Key Project for New Drug Investigations [2012ZX09303008] |
出版者 | SPRINGER FRANCE |
出版地 | PARIS |
ISSN | 0378-7966 |
EISSN | 2107-0180 |
卷号 | 41期号:1页码:79-86 |
DOI | 10.1007/s13318-014-0245-2 |
页数 | 8 |
WOS类目 | Pharmacology & Pharmacy |
WOS研究方向 | Pharmacology & Pharmacy |
WOS记录号 | WOS:000369404700009 |
收录类别 | SCIE ; PUBMED ; SCOPUS |
URL | 查看原文 |
PubMed ID | 25476996 |
SCOPUSEID | 2-s2.0-84956829520 |
通讯作者地址 | [Hu, Guo-Xin]Department of Pharmacology,School of Pharmacy,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China |
Scopus学科分类 | Pharmacology;Pharmacology (medical) |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.wmu.edu.cn/handle/3ETUA0LF/5534 |
专题 | 药学院(分析测试中心) 药学院(分析测试中心)_临床药学与药理系 |
通讯作者 | Hu, Guo-Xin |
作者单位 | 1.Department of Pharmacology,School of Pharmacy,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China; 2.Key Laboratory of Geriatrics,Beijing Hospital,Beijing Institute of Geriatrics,Ministry of Health,Beijing,China |
第一作者单位 | 临床药学与药理系 |
通讯作者单位 | 临床药学与药理系 |
第一作者的第一单位 | 临床药学与药理系 |
推荐引用方式 GB/T 7714 | Pan, Pei-Pei,Weng, Qing-Hua,Zhou, Chen-Jian,et al. The role of CYP2C9 genetic polymorphism in carvedilol O-desmethylation in vitro[J]. EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS,2016,41(1):79-86. |
APA | Pan, Pei-Pei., Weng, Qing-Hua., Zhou, Chen-Jian., Wei, Yan-Li., Wang, Li., ... & Hu, Guo-Xin. (2016). The role of CYP2C9 genetic polymorphism in carvedilol O-desmethylation in vitro. EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS, 41(1), 79-86. |
MLA | Pan, Pei-Pei,et al."The role of CYP2C9 genetic polymorphism in carvedilol O-desmethylation in vitro".EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS 41.1(2016):79-86. |
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