中国科学院大连化学物理研究所机构知识库
Advanced  
DICP OpenIR  > 中国科学院大连化学物理研究所  > 会议论文
学科主题: 物理化学
题名: Glucuronidation of arbidol: identification of human UDP-glucuronosyltransferases and interaction potential
作者: Fang ZZ(房中则) ;  Yang L(杨凌)
会议名称: 9th International Meeting of the International-Society-for-the-Study-of-Xenobiotics
会议日期: 2010-9-4
出版日期: 2010-09-04
会议地点: 土耳其
通讯作者: Ling Yang
部门归属: 十八室
主办者: 国际药物代谢学会
摘要: Arbidol is an antiviral drug indicated for the prevention and treatment of all types of influenza infection and some other kinds of acute respiratory infections. It was marketed in Russia in 1993 and in China in 2006. Previous reports (Wang et al., 2008) have demonstrated that glucuronidation conjugation reaction was a major elimination pathway of arbidol. However, the UDP-glucuronosyltransferases (UGTs) involved in this process remains to be investigated. The present study aimed at identifying unambiguously the UGT isoforms involved in the production of arbidol O-glucuronide. Arbidol O-glucuronide was firstly isolated from a reaction mixture consisting of arbidol and human liver microsomes fortified with UDP-glucuronic acid (UDPGA) and elucidated by HPLC-MS/MS. The kinetic parameters were determined for pooled human liver microsomes (HLMs) and Vmax and Km values were calculated to be 2.03±0.05 nmol/min/mg protein and 8.0±0.7μM respectively. Assessment of a panel of recombinant UGT isoforms revealed the arbidol glucuronosyltransferase activity of UGT1A1, UGT1A3, UGT1A9. The results obtained from kinetic studies and chemical inhibition all demonstrated that UGT1A9 was a predominant UGT isoform involved in the glucuronidation of arbidol in HLM. Considering that UGT1A9 and UGT2B7 could metabolize many clinical drugs, inhibitory effects of arbidol on these two UGT isoforms were investigated. The results demonstrated that arbidol competitively inhibited UGT1A9 and UGT2B7. Ki values were calculated to be 3.5 μM (for UGT1A9) and 0.5 μM (for UGT2B7) when 4-MU was used as substrates. When propofol and 3’-azido-3’-deoxythymidine (AZT) were utilized as substrates for UGT1A9 and UGT2B7 respectively, Ki values were 29.7 μM (for UGT1A9) and 2.8 μM (UGT2B7). All these results were helpful for better understanding of arbidol’s pharmaceutical behaviour and its DDI potential.
语种: 中文
Citation statistics: 
内容类型: 会议论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/114314
Appears in Collections:中国科学院大连化学物理研究所_会议论文

Files in This Item:

There are no files associated with this item.


Recommended Citation:
Fang ZZ,Yang L. Glucuronidation of arbidol: identification of human UDP-glucuronosyltransferases and interaction potential[C]. 见:9th International Meeting of the International-Society-for-the-Study-of-Xenobiotics. 土耳其. 2010-9-4.
Service
 Recommend this item
 Sava as my favorate item
 Show this item's statistics
 Export Endnote File
Google Scholar
 Similar articles in Google Scholar
 [房中则]'s Articles
 [杨凌]'s Articles
CSDL cross search
 Similar articles in CSDL Cross Search
 [房中则]‘s Articles
 [杨凌]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
  Add to CiteULike  Add to Connotea  Add to Del.icio.us  Add to Digg  Add to Reddit 
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Powered by CSpace