Correlations between the enantio- and regio-selective metabolisms of warfarin. (January 2017)

• Record Type: Journal Article
• Authors: Takahashi, Harumi; Ohara, Minami; Shibata, Soichi; Lee, Ming Ta Michael; Cavallari, Larisa H; Nutescu, Edith A; Scordo, Maria G; Pengo, Vittorio; Padrini, Roberto; Atsuda, Koichiro; Matsubara, Hajime; Chen, Yuan Tsong; Echizen, Hirotoshi
• Is Part Of: Pharmacogenomics. Volume 18:Number 2(2017)
• Page Start: 133
• Page End: 142
• Publication Date: 2017-01
• Subjects: CYP1A2 -- CYP2C9 -- CYP3A4 -- metabolism -- transcriptional factors -- warfarin enantiomers; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs-2016-0149
• Languages: English
• ISSNs: 1462-2416

Abstract

Aim: 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.Conclusion: Metabolic activities of CYP2C9, CYP1A2 and CYP3A4 may be regulated by common transcriptional mechanism(s).