The role of CYP2C9 genetic polymorphism in carvedilol O-desmethylation in vitro

doi:10.1007/s13318-014-0245-2

科研成果详情

题名	The role of CYP2C9 genetic polymorphism in carvedilol O-desmethylation in vitro
作者	Pan, Pei-Pei 1; Weng, Qing-Hua 1; Zhou, Chen-Jian 1; Wei, Yan-Li1; Wang, Li 1; Dai, Da-Peng 2; Cai, Jian-Ping 2; Hu, Guo-Xin1
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	被引频次：11[WOS] [WOS记录] [WOS相关记录]
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.