Optimized assays for human UDP-glucuronosyltransferase (UGT) activities: altered alamethicin concentration and utility to screen for UGT inhibitors

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Robert L WalskyTheunis C Goosen

Abstract

The measurement of the effect of new chemical entities on human UDP-glucuronosyltransferase (UGT) marker activities using in vitro experimentation represents an important experimental approach in drug development to guide clinical drug-interaction study designs or support claims that no in vivo interaction will occur. Selective high-performance liquid chromatography-tandem mass spectrometry functional assays of authentic glucuronides for five major hepatic UGT probe substrates were developed: β-estradiol-3-glucuronide (UGT1A1), trifluoperazine-N-glucuronide (UGT1A4), 5-hydroxytryptophol-O-glucuronide (UGT1A6), propofol-O-glucuronide (UGT1A9), and zidovudine-5'-glucuronide (UGT2B7). High analytical sensitivity permitted characterization of enzyme kinetic parameters at low human liver microsomal and recombinant UGT protein concentration (0.025 mg/ml), which led to a new recommended optimal universal alamethicin activation concentration of 10 μg/ml for microsomes. Alamethicin was not required for recombinant UGT incubations. Apparent enzyme kinetic parameters, particularly for UGT1A1 and UGT1A4, were affected by nonspecific binding. Unbound intrinsic clearance for UGT1A9 and UGT2B7 increased significantly after addition of 2% bovi...Continue Reading

References

Jan 5, 2002·Drug Metabolism Reviews·M B FisherS A Wrighton
Jun 8, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Khalid M Alkharfy, Reginald F Frye
Mar 8, 2003·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S KrishnaswamyM H Court
May 21, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Matthew G SoarsSteven A Wrighton
Jun 20, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Thorir D BjornssonUNKNOWN FDA Center for Drug Evaluation and Research (CDER)
Jan 8, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Matthew G SoarsSteven A Wrighton
May 25, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Robert L Walsky, R Scott Obach
Jul 20, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Soundararajan KrishnaswamyMichael H Court
Aug 12, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·J Andrew WilliamsSimon E Ball
Mar 23, 2005·Pharmacology & Therapeutics·Tony K L KiangThomas K H Chang
Apr 23, 2005·Proceedings of the National Academy of Sciences of the United States of America·Nikhil K BasuIda S Owens
Jun 28, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jonathan N BaumanJ Andrew Williams
Sep 6, 2005·Pharmacogenetics and Genomics·Peter I MackenzieDaniel W Nebert
Mar 28, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Andrew RowlandJohn O Miners
Jul 1, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Giuseppe ToffoliSergio Frustaci
May 2, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Theunis C GoosenCho-Ming Loi
Jul 11, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ryoichi FujiwaraTsuyoshi Yokoi
Oct 6, 2007·Expert Opinion on Drug Metabolism & Toxicology·Hongjian ZhangA David Rodrigues
Feb 27, 2008·Journal of Pharmaceutical Sciences·Nigel J WatersBindi Sohal
Jun 6, 2008·Journal of Clinical Pharmacology·J Andrew WilliamsSteven A Wrighton
Aug 23, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Katriina ItäahoMoshe Finel
Sep 26, 2008·Basic & Clinical Pharmacology & Toxicology·Hiroko TakahashiYoshihiro Takeuchi
May 29, 2009·Journal of Pharmaceutical Sciences·Ryoichi FujiwaraTsuyoshi Yokoi
Jun 3, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Oranun KerdpinJohn O Miners
Oct 24, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yong LiuMark J Ratain

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Citations

Oct 23, 2013·The International Journal of Biochemistry & Cell Biology·Sushrut JangiSimon Robson
Jan 11, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Katherine L GillAleksandra Galetin
Jan 8, 2014·Expert Opinion on Drug Metabolism & Toxicology·Li Di
Feb 28, 2016·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Shalenie P den Braver-SewradjJ Chris Vos
Mar 8, 2016·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Melanie A LaddJohn W Nichols
May 18, 2013·Chemistry & Biodiversity·László KredicsBalázs Leitgeb
Sep 9, 2015·Journal of Medicinal Chemistry·Kentaro FutatsugiBryan Goodwin
Apr 1, 2016·Chemical Research in Toxicology·Ting-Ting CaiRobert J Turesky
Jul 30, 2015·The Journal of Steroid Biochemistry and Molecular Biology·Roope A KallionpääMoshe Finel
Jun 9, 2015·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Larry HouseMark J Ratain
Feb 26, 2015·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Cui GaoYueming Ma
Dec 31, 2014·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Darja Gramec SkledarMoshe Finel
Sep 13, 2013·Drug Metabolism and Pharmacokinetics·Kazuhiro TetsukaJeffrey N Masters
Feb 3, 2015·Cell Reports·Jeroen R P M StratingFrank J M van Kuppeveld
Feb 17, 2015·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Julieta GradinaruSerge Rudaz
Mar 12, 2015·Drug Metabolism and Pharmacokinetics·Shingo OdaMiki Nakajima
Jan 26, 2016·British Journal of Clinical Pharmacology·Kathleen M KnightsJohn O Miners
Apr 8, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tonika BohnertUNKNOWN International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) Victim Drug-Drug Interactions Working
Mar 31, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rao MukkavilliRitu Aneja
May 5, 2017·Drug Metabolism Reviews·S Cyrus KhojastehGrover Miller
Jul 12, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Guiyuan HeLing Yang
Feb 10, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Byoung Hoon YouYoung Hee Choi
Sep 5, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Gurinder WaliaMichael W H Coughtrie
Jul 30, 2014·Antimicrobial Agents and Chemotherapy·Xiaoyan PangXiaoyan Chen
Nov 10, 2018·The Journal of Pharmacology and Experimental Therapeutics·Aaron M TeitelbaumAllan E Rettie
Sep 9, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kimberly LaphamAmit S Kalgutkar
Jul 17, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Attarat PattanawongsaJohn O Miners
Apr 5, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Verawan UchaipichatJohn O Miners
Aug 24, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jana C PrechtThomas E Mürdter
Sep 1, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Brandon T GuffordMary F Paine

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