Role of cytochrome P450 2C9 and an allelic variant in the 4'-hydroxylation of (R)- and (S)-flurbiprofen

Biochemical Pharmacology
T S TracyK R Korzekwa


Flurbiprofen is a chiral non-steroidal anti-inflammatory drug used in the treatment of pain or inflammation. The primary routes of biotransformation for (R)- and (S)-flurbiprofen are oxidation (presumably cytochrome P450) and conjugation. To date, the specific cytochrome P450 (P450) involved in the oxidative metabolism of this compound (specifically 4'-hydroxylation) has not been elucidated. Experiments were conducted to characterize the kinetic parameters (Km and Vmax) for the 4'-hydroxylation of (R)- and (S)-flurbiprofen in human liver microsomes, to determine if enantiomeric interactions occur when both enantiomers are present, and to identify the specific P450 form(s) involved in this reaction. In human liver microsomes, the Km and Vmax (mean +/- SD) for (R)-4'-hydroxy-flurbiprofen formation were 3.1 +/- 0.8 microM and 305 +/- 168 protein)-1, respectively. In comparison, the Km and Vmax (mean +/- SD) for (S)-4'-hydroxy-flurbiprofen formation were 1.9 +/- 0.4 microM and 343 +/- 196 protein-1, respectively. Enantiomeric interaction studies revealed a decrease in Km and Vmax for both enantiomers and an apparent loss of stereoselectivity. Racemic-warfarin, tolbutamide, alpha-naphthoflavone and erythr...Continue Reading


Nov 1, 1978·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·P C RisdallB Marchant
Jan 1, 1979·Methods in Enzymology·W W Cleland
Jan 1, 1991·Methods in Enzymology·F J GonzalezH V Gelboin
Jan 1, 1990·Chirality·M P Knadler, S D Hall
Mar 24, 1986·The American Journal of Medicine·T G Kantor
Aug 1, 1988·Journal of Pharmaceutical Sciences·F JamaliA S Russell
May 1, 1987·Biopharmaceutics & Drug Disposition·G J SzpunarJ G Wagner
Sep 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·P B WatkinsP S Guzelian


Dec 17, 2009·JAMA : the Journal of the American Medical Association·Robert C GreenTarenflurbil Phase 3 Study Group
Jun 7, 2006·Veterinary Research Communications·L IgarzaH Zeballos
Jul 8, 2009·Applied Biochemistry and Biotechnology·Sepuri Asha, Maravajhala Vidyavathi
Dec 5, 2002·Archives of Biochemistry and Biophysics·David F V Lewis
Feb 1, 2003·Archives of Biochemistry and Biophysics·J M HutzlerT S Tracy
Mar 10, 1998·Research in Veterinary Science·W M Zweers-ZeilmakerA S Van Miert
Apr 4, 1998·Thrombosis Research·Z Y ZhangL S Kaminsky
Dec 29, 2000·Journal of Chromatography. B, Biomedical Sciences and Applications·J M HutzlerT S Tracy
Jul 18, 2001·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·J M HutzlerT S Tracy
Jul 15, 1998·British Journal of Clinical Pharmacology·J O Miners, D J Birkett
May 23, 1998·Journal of Veterinary Pharmacology and Therapeutics·W M Zweers-ZeilmakerR F Witkamp
Oct 11, 2012·Pharmacogenetics and Genomics·Lei HuLan Fan
Aug 25, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Vikas KumarJan L Wahlstrom
Apr 2, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Vikas KumarT S Tracy
Jul 27, 2010·Applied and Environmental Microbiology·Jessica AmadioCormac D Murphy
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·J H Lin, A Y Lu
Jan 11, 2003·Journal of Clinical Pharmacology·Craig R LeeJ A Goldstein
Nov 14, 2007·BMC Evolutionary Biology·Erica J ReschlyMatthew D Krasowski
Aug 29, 2001·Clinical Pharmacokinetics·H Takahashi, H Echizen
Mar 21, 2009·Analytical and Bioanalytical Chemistry·Raluca-Ioana Stefan-van StadenHassan Y Aboul-Enein
Oct 14, 2014·Drug and Chemical Toxicology·Taygun Timocin, Hasan B Ila
Oct 14, 2003·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·B K PatelA J Hutt
Apr 2, 1998·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·C E OngC R Bhasker
May 9, 2002·Drug Metabolism Reviews·Slobodan Rendic
Mar 8, 2005·Drug Metabolism Reviews·Haiping HaoJianguo Sun
Oct 24, 2006·British Journal of Clinical Pharmacology·N K ZgheibR A Branch
Sep 3, 2014·Biotechnology Letters·Cormac D Murphy
Jun 8, 2004·The Journal of Biological Chemistry·Michael R WesterEric F Johnson
Feb 2, 2018·Journal of Personalized Medicine·Lindsay M HendersonKenneth E Thummel
Apr 17, 2003·European Journal of Clinical Pharmacology·Craig R LeeJ A Goldstein
Aug 12, 2005·The Journal of Pharmacology and Experimental Therapeutics·Xue-Qing LiTommy B Andersson

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