Abstract
Budesonide, a glucocorticoid with a high first-pass metabolism, is used for the oral treatment of inflammatory bowel disease. Cytochrome P450 3A4 (CYP3A4) is an enzyme involved in the metabolism of numerous drugs, including budesonide. Since inhibition or induction of CYP3A4 is often the cause of drug-drug interactions we analyzed how budesonide affects the activity and expression of this enzyme. CYP3A4 activity was assessed by the metabolism of a luminogenic substrate (luciferin-benzylether) using recombinant human CYP3A4 protein. We observed no inhibition of the metabolism in the presence of budesonide at concentrations up to 25 microM. Induction experiments in human LS180 colon carcinoma cells showed an increased expression of CYP3A4 mRNA after budesonide treatment. Transactivation assays revealed that budesonide activates the CYP3A4 promoter via the pregnane X receptor (PXR). In mice, oral budesonide administration (25mg/kg) for 4 days induced the murine homolog Cyp3a11 in the intestine 3-fold, whereas liver expression was notably less influenced. In knockout mice devoid of PXR, budesonide-mediated inductions were reduced compared to wild-type mice. In conclusion, we could demonstrate that budesonide is not an efficient inh...Continue Reading
References
Sep 3, 1998·The Journal of Clinical Investigation·J M LehmannS A Kliewer
Dec 5, 1998·Clinical Pharmacokinetics·J H Lin, A Y Lu
Apr 5, 2000·The Journal of Biological Chemistry·L B MooreS A Kliewer
Apr 12, 2001·The Journal of Biological Chemistry·A GeickO Burk
Jul 27, 2001·Fundamental & Clinical Pharmacology·J CortijoE J Morcillo
Oct 27, 2001·The Journal of Biological Chemistry·Sabine Gerbal-ChaloinPatrick Maurel
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Dec 7, 2002·European Journal of Gastroenterology & Hepatology·Staffan EdsbäckerPer Wollmer
Jan 23, 2003·The Journal of Pharmacology and Experimental Therapeutics·Janne HukkanenJukka Hakkola
Feb 8, 2003·Biochimica Et Biophysica Acta·J M PascussiM J Vilarem
Sep 10, 2004·Clinical Pharmacokinetics·Staffan Edsbäcker, Tommy Andersson
Feb 24, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Karin DilgerUlrich Beuers
May 28, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Xingguo ChengCurtis D Klaassen
Dec 31, 2005·International Journal of Pharmaceutics·Mingji JinKen-ichi Miyamoto
Dec 21, 2006·British Journal of Pharmacology·A MaierH Gutmann
Apr 3, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Chuang LuSuresh K Balani
Aug 19, 2008·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Janeric SeidegårdOlof Borgå
Citations
Nov 12, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yongmei PanPeter W Swaan
Mar 7, 2012·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Chiara RoncoroniPaolo Ciana
Apr 30, 2010·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Christoph DornClaus Hellerbrand
Aug 23, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Akira HondaYasushi Matsuzaki
Jan 1, 2014·Alimentary Pharmacology & Therapeutics·T H KarlsenK M Boberg
Sep 1, 2015·The Journal of Steroid Biochemistry and Molecular Biology·M R WilkensA L Lifschitz
Dec 3, 2014·Toxicology Letters·Marcin RatajewskiJarosław Dastych
Dec 18, 2013·Molecular Aspects of Medicine·Anna BaghdasaryanMichael Trauner
Mar 17, 2017·Inflammatory Bowel Diseases·Aze WilsonRichard B Kim
Jul 22, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Nancy ChenDevin Welty
Aug 11, 2011·Inflammatory Bowel Diseases·Jürgen GlasStephan Brand
Mar 25, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Zufei ZhangJashvant D Unadkat
Dec 17, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Mélina DaniVincent Pichette
Dec 12, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ioannis PapageorgiouJashvant D Unadkat
Oct 7, 2016·Journal of Biochemical and Molecular Toxicology·Hui LiNathan J Cherrington
Dec 2, 2020·Medical Hypotheses·Hanjun Lee
Jul 17, 2012·Chemical Research in Toxicology·Amy M SharmaJack Uetrecht