PMID: 8946477Oct 1, 1996Paper

CYP2D6 is the principal cytochrome P450 responsible for metabolism of the histamine H1 antagonist promethazine in human liver microsomes

Pharmacogenetics
K NakamuraT Kamataki

Abstract

To determine which cytochrome P450 form is involved in the promethazine [10-(2-dimethylaminopropyl) phenothiazine] metabolism, in vitro analysis using human liver microsomes were performed. Promethazine was mainly biotransformed to ring-hydroxylated, S-oxidized and N-demethylated metabolites. The promethazine hydroxylase in human liver microsomes was inhibited by SKF-525A, propranolol, sparteine, quinidine and anti-CYP2D6 serum suggesting involvement of a P450 related to CYP2D6. Lineweaver-Burk plots for the hydroxylation, S-oxidation and N-demethylation indicated that the hydroxylation occurred with a low K(m) value in human liver microsomes. Microsomes from genetically-engineered human B-lymphoblastoid cells expressing CYP2D6 hydroxylated promethazine most efficiently as compared to other P450 forms, indicating that it was the principal P450 responsible for the metabolism of promethazine in human liver microsomes. The inhibition of CYP2D6-catalysed bufuralol 1'-hydroxylase by various histamine H3 antagonists including promethazine suggested that promethazine and some other histamine H1 antagonists could be inhibitors of this P450 in human liver microsomes.

Citations

Aug 13, 2008·Analytical and Bioanalytical Chemistry·Ulrich M ZangerMatthias Schwab
Feb 22, 2011·European Journal of Drug Metabolism and Pharmacokinetics·Siamak Cyrus KhojastehAnthony Y H Lu
Dec 4, 2003·Bioorganic & Medicinal Chemistry·Shahriar Haji-MomenianMilton L Brown
Feb 13, 2001·Journal of Veterinary Pharmacology and Therapeutics·I A WasfiI M Barezaig
May 5, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kostandinos SiderasMatthew P Goetz
Oct 13, 2009·Clinical Pharmacokinetics·Shu-Feng Zhou
Nov 12, 2009·Clinical Pharmacokinetics·Shu-Feng Zhou
Aug 12, 1999·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·A G Renwick
Jun 12, 2009·Drug Metabolism Reviews·Shu-Feng ZhouBalram Chowbay
Aug 26, 1999·Drug Metabolism Reviews·S Ekins, S A Wrighton
May 9, 2002·Drug Metabolism Reviews·Slobodan Rendic
Feb 2, 2016·Drug Metabolism Reviews·Petra MatalováPavel Anzenbacher
Jan 20, 2010·Journal of Forensic and Legal Medicine·Aya MatsusueShin-Ichi Kubo
Dec 12, 2007·Psychosomatics·Scott WilliamsNeil B Sandson
Jun 11, 2015·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·A S YoussefS Nagar
Nov 8, 2007·Pain Practice : the Official Journal of World Institute of Pain·Adriana FosterZixuan Wang
Jul 27, 2015·Journal of Perianesthesia Nursing : Official Journal of the American Society of PeriAnesthesia Nurses·Ling-Ling ZhuQuan Zhou
Dec 25, 2004·Drug Metabolism and Pharmacokinetics·Yoshihiko FunaeToyoko Hiroi
May 23, 2007·Australasian Psychiatry : Bulletin of Royal Australian and New Zealand College of Psychiatrists·James ScottNatalie O'Brien
Jan 1, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Martin LitzenburgerRita Bernhardt
Sep 14, 2006·Pharmacological Reviews·Sharon J Gardiner, Evan J Begg
May 13, 1998·British Journal of Clinical Pharmacology·H H KupferschmidtS Krähenbühl
Oct 5, 2017·Prion·Pardis Tabaee DamavandiRichard W Pickersgill
Oct 6, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tomoko AkutsuKan Chiba
Oct 10, 2009·Renal Failure·Nelson LeungVesna D Garovic
Sep 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Huayan LiuYongzhi Li
Oct 23, 2019·Substance Abuse : Official Publication of the Association for Medical Education and Research in Substance Abuse·Avik ChatterjeeTravis P Baggett
Nov 24, 2019·Surgical Oncology Clinics of North America·Rodney A GabrielRuth S Waterman
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Babiker M Eh-Haj

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