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题名: Enantioselective Inhibition of Carprofen Towards UDP-glucuronosyltransferase (UGT) 2B7
作者: Fang, Zhong-Ze1;  Wang, Haina2;  Cao, Yun-Feng3;  Sun, Dong-Xue4;  Wang, Li-Xuan5, 6;  Hong, Mo4;  Huang, Ting3;  Chen, Jian-Xing3;  Zeng, Jia3
关键词: carprofen ;  enantioselective inhibition ;  UDP-glucuronosyltransferase (UGT)
刊名: CHIRALITY
发表日期: 2015-03-01
DOI: 10.1002/chir.22412
卷: 27, 期:3, 页:189-193
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine ;  Physical Sciences
类目[WOS]: Chemistry, Medicinal ;  Chemistry, Analytical ;  Chemistry, Organic ;  Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy ;  Chemistry
英文摘要: UDP-glucuronosyltransferases (UGTs)-catalyzed glucuronidation conjugation reaction plays an important role in the elimination of many important clinical drugs and endogenous substances. The present study aims to investigate the enantioselective inhibition of carprofen towards UGT isoforms. In vitro a recombinant UGT isoforms-catalyzed 4-methylumbelliferone (4-MU) glucuronidation incubation mixture was used to screen the inhibition potential of (R)-carprofen and (S)-carprofen towards multiple UGT isoforms. The results showed that (S)-carprofen exhibited stronger inhibition potential than (R)-carprofen towards UGT2B7. However, no significant difference was observed for the inhibition of (R)-carprofen and (S)-carprofen towards other UGT isoforms. Furthermore, the inhibition kinetic behavior was compared for the inhibition of (S)-carprofen and (R)-carprofen towards UGT2B7. A Lineweaver-Burk plot showed that both (S)-carprofen and (R)-carprofen exhibited competitive inhibition towards UGT2B7-catalyzed 4-MU glucuronidation. The inhibition kinetic parameter (K-i) was calculated to be 7.0M and 31.1M for (S)-carprofen and (R)-carprofen, respectively. Based on the standard for drug-drug interaction, the threshold for (S)-carprofen and (R)-carprofen to induce a drug-drug interaction is 0.7M and 3.1M, respectively. In conclusion, enantioselective inhibition of carprofen towards UDP-glucuronosyltransferase (UGT) 2B7 was demonstrated in the present study. Using the in vitro inhibition kinetic parameter, the concentration threshold of (S)-carprofen and (R)-carprofen to possibly induce the drug-drug interaction was obtained. Therefore, clinical monitoring of the plasma concentration of (S)-carprofen is more important than (R)-carprofen to avoid a possible drug-drug interaction between carprofen and the drugs mainly undergoing UGT2B7-catalyzed metabolism. Chirality 27:189-193, 2015. (c) 2014 Wiley Periodicals, Inc.
关键词[WOS]: HUMAN SERUM-ALBUMIN ;  PHARMACOKINETICS ;  GLUCURONIDATION ;  BINDING ;  ENANTIOMERS
语种: 英语
WOS记录号: WOS:000350137200001
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/146019
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Tianjin Med Univ, Sch Publ Hlth, Dept Toxicol, Tianjin 300070, Peoples R China
2.Shandong Univ, Coll Pharmaceut Sci, Jinan 250100, Peoples R China
3.Shanghai Inst Planned Parenthood Res, Shanghai Engineer & Technol Res Ctr Reprod Hlth D, Key Lab Contracept & Devices Res NPFPC, Shanghai, Peoples R China
4.Shenyang Pharmaceut Univ, Sch Tradit Chinese Med, Shenyang, Peoples R China
5.Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian, Peoples R China
6.Liaoning Med Univ, Affiliated Hosp 1, Dalian, Peoples R China

Recommended Citation:
Fang, Zhong-Ze,Wang, Haina,Cao, Yun-Feng,et al. Enantioselective Inhibition of Carprofen Towards UDP-glucuronosyltransferase (UGT) 2B7[J]. CHIRALITY,2015,27(3):189-193.
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