Colchicine biotransformation by human liver microsomes. Identification of CYP3A4 as the major isoform responsible for colchicine demethylation

Biochemical Pharmacology
T TateishiA J Wood

Abstract

Colchicine disposition involves both active biliary and renal excretion of parent drug, and at least in mammals a substantial fraction undergoes hepatic demethylation prior to excretion. We investigated the biotransformation of [3H]colchicine in a panel of microsomal preparations obtained from sixteen human liver samples. The production rate of the main metabolites of colchicine's 3-demethylcolchicine (3DMC) and 2-demethylcolchicine (2DMC), was linear in relation to incubation time, cytochrome (P450) content, and substrate concentration. Following the incubation of colchicine (5 nM) with microsomes in the presence of an NADPH-generating system for 60 min, 9.8% and 5.5% of the substrate were metabolized to 3DMC and 2DMC, respectively. The formation rate of colchicine metabolites exhibited a marked variation between the different microsomal preparations. The formation rates of both colchicine metabolites were correlated significantly with nifedipine oxidase activity, a marker of CYP3A4 activity (r = 0.96, P < 0.001), but not with the metabolic markers of CYP2A6, CYP2C19, CYP2C9, CYP2D6, and CYP2E1 activities. Chemical inhibition of CYP3A4 by preincubation with gestodene (40 microM) or troleandomycin (40 microM) reduced the format...Continue Reading

References

Sep 24, 1977·British Medical Journal·M Levy, M Eliakim
Nov 1, 1977·Annals of Internal Medicine·M RavidI Kedar
May 1, 1992·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·K V SpeegD Muirhead
Dec 1, 1991·Seminars in Arthritis and Rheumatism·C PuttermanM Levy
Jul 1, 1990·Chemical Research in Toxicology·F P Guengerich
Jun 30, 1988·The New England Journal of Medicine·D KershenobichM Rojkind
Dec 1, 1987·Arthritis and Rheumatism·L TafiG Bartolozzi
Apr 17, 1986·The New England Journal of Medicine·D ZemerJ Gafni
Dec 4, 1986·The New England Journal of Medicine·M M KaplanK A Eagen
Nov 1, 1974·Hoppe-Seyler's Zeitschrift für physiologische Chemie·M SchönhartingG Siebert
Jan 1, 1974·Seminars in Arthritis and Rheumatism·S L Wallace
Sep 26, 1974·The New England Journal of Medicine
Apr 1, 1994·Therapeutic Drug Monitoring·A SabouraudJ M Scherrmann

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Citations

Jul 8, 2009·Applied Biochemistry and Biotechnology·Sepuri Asha, Maravajhala Vidyavathi
May 22, 2002·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Z DvorakP Maurel
Jul 3, 2003·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Beate BittnerChristophe Flament
Jul 12, 2005·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·I F N HungK Y Yuen
Feb 5, 2009·European Heart Journal·Massimo ImazioYehuda Adler
Nov 1, 2002·Clinical Neuropharmacology·Wei-Chih HsuHou-Chang Chiu
Sep 8, 2005·Southern Medical Journal·Vincent C C ChengK Y Yuen
Jul 17, 2004·Chemical & Pharmaceutical Bulletin·Toshimasa TanakaYoshio Yamamoto
Oct 7, 2009·Future Cardiology·Massimo ImazioYehuda Adler
Jan 6, 2001·Acta Universitatis Palackianae Olomucensis Facultatis Medicae·Z DvorákP Maurel
Apr 8, 2006·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Martin Modrianský, Zdenĕk Dvorák
Apr 11, 2015·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Philip W PeakeZoltan H Endre
Feb 5, 2016·Chemical Research in Toxicology·Xiucai GuoJiang Zheng
Dec 4, 2015·Future Cardiology·Massimo Imazio, Fiorenzo Gaita
May 9, 2002·Drug Metabolism Reviews·Slobodan Rendic
Jul 1, 2010·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Yaron FinkelsteinYedidia Bentur
Oct 26, 2010·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Virginie MontielPhilippe Hantson
Sep 1, 2008·Expert Review of Clinical Pharmacology·Guillaume DumaisPatrick du Souich
May 26, 2005·The Annals of Pharmacotherapy·Gamze AlayliElif B Menekşe
Apr 25, 2017·Critical Reviews in Biotechnology·Kashyap Kumar DubeyPratyoosh Shukla
Jul 2, 2005·Bioorganic & Medicinal Chemistry Letters·Yong-Hua WangLing Yang
Dec 29, 2016·Anti-cancer Drugs·Ashok KumarDilip M Mondhe
Apr 22, 2015·Organic & Biomolecular Chemistry·Baljinder SinghRam A Vishwakarma
Aug 15, 2009·Current Opinion in Neurology·Ralph W Kuncl
Jan 7, 2010·Journal of Clinical Rheumatology : Practical Reports on Rheumatic & Musculoskeletal Diseases·Peter J SebenyAnuradha Ganesan
Jan 30, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Lin XuAndreas Harsch
Nov 8, 2014·Journal of the American Animal Hospital Association·Amber McAlisterSean P McDonough
Jul 2, 2019·Chemical Biology & Drug Design·Joanna KurekPiotr Przybylski
Mar 2, 2016·Pediatric Emergency Care·Demet AlaygutFusun Dilara Icagasioglu
Dec 1, 2004·Therapeutic Drug Monitoring·Jonathan S SussmanLeslie M Shaw
Jul 1, 1999·Addiction Biology·A K ChoY Kumagai
Apr 16, 2014·American Journal of Therapeutics·Zeenat Yousuf BhatElizabeth Wilpula
Aug 25, 2020·SN Comprehensive Clinical Medicine·Christodoulos PapadopoulosVassilios P Vassilikos
Mar 15, 2008·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·E A PartridgeD W Roberts
Oct 21, 2004·The Annals of Pharmacotherapy·Florence RollotPhilippe Blanche
Sep 27, 2007·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·A D McCormickD W Roberts

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