title: Correlations between the enantio- and regio-selective metabolisms of warfarin.
abstract: OBJECTIVE
  To clarify whether the activities of multiple CYPs associated with warfarin metabolism would be correlated with each other.
  
  
  METHODS
  Oral clearances (CLpo) of warfarin enantiomers were estimated in 378 Chinese, Caucasians and African-Americans. The partial metabolic clearances (CLm) for 7-hydroxywarfarin enantiomers were also measured. In addition, CLpo and CLm were determined in a patient on warfarin and rifampicin.
  
  
  RESULTS
  Correlations between CLpo for warfarin enantiomers existed across the three populations. In addition, there was a significant correlation between the CLm for 7-hydroxylation of warfarin enantiomers. Under induced conditions by rifampicin, there were significant correlations between the enantio- and regio-selective metabolisms of warfarin.
  
  
  CONCLUSIONS
  Metabolic activities of CYP2C9, CYP1A2 and CYP3A4 may be regulated by common transcriptional mechanism(s).
authors.affiliation: Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Ohara
authors.affiliation: Department of Pharmacy, Kitasato Institute Hospital, Kitasato University, Tokyo, Japan.
authors.forename: Soichi
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Geisinger Health System, Danville, PN, USA.|Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Ming Ta Michael
authors.initials: MT
authors.lastname: Lee
authors.affiliation: Department of Pharmacotherapy & Translational Research & Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA.
authors.forename: Larisa H
authors.initials: LH
authors.lastname: Cavallari
authors.affiliation: Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Edith A
authors.initials: EA
authors.lastname: Nutescu
authors.affiliation: Department of Medical Sciences, Clinical Pharmacology, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Scordo
authors.affiliation: Department of Cardiothoracic & Vascular Sciences, University of Padova, Padova, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Pengo
authors.affiliation: Department of Medicine DIMED, University of Padova, Padova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Padrini
authors.affiliation: Department of Pharmacy, Kitasato University Hospital, Kanagawa, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Atsuda
authors.affiliation: Department of Pharmacy, Kitasato Institute Hospital, Kitasato University, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Matsubara
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Yuan Tsong
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Department of Pharmacotherapy, Meiji Pharmaceutical University, Tokyo, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Echizen
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000925:Anticoagulants / Q000737:chemistry / Q000378:metabolism*; D044466:Asian People / Q000235:genetics*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013237:Stereoisomerism; D014859:Warfarin / Q000737:chemistry / Q000378:metabolism*; D044465:White People / Q000235:genetics*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human
keywords: CYP1A2; CYP2C9; CYP3A4; metabolism; transcriptional factors; warfarin enantiomers