DICP OpenIR
Enantioselective Inhibition of Carprofen Towards UDP-glucuronosyltransferase (UGT) 2B7
Fang, Zhong-Ze1; Wang, Haina2; Cao, Yun-Feng3; Sun, Dong-Xue4; Wang, Li-Xuan5,6; Hong, Mo4; Huang, Ting3; Chen, Jian-Xing3; Zeng, Jia3
KeywordCarprofen Enantioselective Inhibition Udp-glucuronosyltransferase (Ugt)
Source PublicationCHIRALITY
2015-03-01
DOI10.1002/chir.22412
Volume27Issue:3Pages:189-193
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine ; Physical Sciences
WOS SubjectChemistry, Medicinal ; Chemistry, Analytical ; Chemistry, Organic ; Pharmacology & Pharmacy
WOS Research AreaPharmacology & Pharmacy ; Chemistry
WOS KeywordHUMAN SERUM-ALBUMIN ; PHARMACOKINETICS ; GLUCURONIDATION ; BINDING ; ENANTIOMERS
AbstractUDP-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.
Language英语
WOS IDWOS:000350137200001
Citation statistics
Cited Times:16[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/146019
Collection中国科学院大连化学物理研究所
Affiliation1.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
GB/T 7714
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.
APA Fang, Zhong-Ze.,Wang, Haina.,Cao, Yun-Feng.,Sun, Dong-Xue.,Wang, Li-Xuan.,...&Zeng, Jia.(2015).Enantioselective Inhibition of Carprofen Towards UDP-glucuronosyltransferase (UGT) 2B7.CHIRALITY,27(3),189-193.
MLA Fang, Zhong-Ze,et al."Enantioselective Inhibition of Carprofen Towards UDP-glucuronosyltransferase (UGT) 2B7".CHIRALITY 27.3(2015):189-193.
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