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Inhibitory potential of chlormadinone acetate (CMA) on five important UDP-glucuronosyltransferases in human liver
Huang, Ting2; Fang, Zhong-Ze1,3; Zhang, Yan-Yan1,3; Zhu, Liang-Liang1,3; Feng, Ling-Lin2; Zheng, Wei2; Cao, Yun-Feng4; Sun, Dong-Xue4; Yang, Ling1
Source PublicationPHARMAZIE
2011-03-01
DOI10.1691/ph.2011.0745
Volume66Issue:3Pages:212-215
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine ; Physical Sciences
WOS SubjectChemistry, Medicinal ; Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS Research AreaPharmacology & Pharmacy ; Chemistry
WOS KeywordDRUG-DRUG INTERACTIONS ; HUMAN-IMMUNODEFICIENCY-VIRUS ; GLUCURONIDATION ; ZIDOVUDINE ; 3'-AZIDO-3'-DEOXYTHYMIDINE ; MICROSOMES ; BELARA(R) ; VITRO ; 2B7
AbstractChlormadinone acetate (CMA), a derivative of 17-a-hydroxyprogesterone, has been widely used as an orally effective progestogen in hormone replacement therapy (HRT). Glucuronidation catalyzed by UDP-glucuronosyltransferases (UGTs) is one of the major steps responsible for the metabolism of many drugs, environmental chemicals and endogenous compounds. Pharmacokinetic behaviours of drugs could be altered by inhibition of these UGT isoforms, and the search for drugs that potentially inhibit these UGT isoforms is very significant from a clinical point of view. In the present study, inhibition of five important UGT isoforms in human liver (UGT1A1, 1A3, 1A6, 1A9 and 2B7) by CMA was investigated using 4-MU as nonspecific substrate and recombinant UGT isoforms as enzyme sources. The results showed that CMA exhibited inhibitory effects on UGT1A3 (IC(50) = 8.6 +/- 1.4 mu M) and UGT2B7 (IC(50) = 14.2 +/- 3.8 mu M), with other UGT isoforms negligibly influenced. Lineweaver-Burk and Dixon plots showed that CMA noncompetitively inhibited UGT1A3 and UGT2B7. The K(i) value was calculated to be 36.9 mu M and 4.1 mu M for UGT1A3 and UGT2B7, respectively. Considering that UGT1A3 and UGT2B7 are involved in the metabolism of many drugs, special attentions should be paid when CMA was co-administered with the drugs which mainly underwent UGT1A3, 2B7-mediated metabolism.
Language英语
WOS IDWOS:000290597700012
Citation statistics
Cited Times:18[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/141704
Collection中国科学院大连化学物理研究所
Affiliation1.Chinese Acad Sci, Lab Pharmaceut Resource Discovery, Dalian Inst Chem Phys, Dalian 116023, Peoples R China
2.Shanghai Inst Planned Parenthood Res, Natl Populat & Family Planning Key Lab Contracept, Shanghai, Peoples R China
3.Chinese Acad Sci, Grad Sch, Beijing, Peoples R China
4.Shenyang Pharmaceut Univ, Sch Tradit Chinese Med, Shenyang, Peoples R China
Recommended Citation
GB/T 7714
Huang, Ting,Fang, Zhong-Ze,Zhang, Yan-Yan,et al. Inhibitory potential of chlormadinone acetate (CMA) on five important UDP-glucuronosyltransferases in human liver[J]. PHARMAZIE,2011,66(3):212-215.
APA Huang, Ting.,Fang, Zhong-Ze.,Zhang, Yan-Yan.,Zhu, Liang-Liang.,Feng, Ling-Lin.,...&Yang, Ling.(2011).Inhibitory potential of chlormadinone acetate (CMA) on five important UDP-glucuronosyltransferases in human liver.PHARMAZIE,66(3),212-215.
MLA Huang, Ting,et al."Inhibitory potential of chlormadinone acetate (CMA) on five important UDP-glucuronosyltransferases in human liver".PHARMAZIE 66.3(2011):212-215.
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