Correlations between the enantio- and regio-selective metabolisms of warfarin-Reference-Cited by-同舟云学术

Correlations between the enantio- and regio-selective metabolisms of warfarin

Published:2017-01 Issue:2 Volume:18 Page:133-142
ISSN:1462-2416
Container-title:Pharmacogenomics
language:en
Short-container-title:Pharmacogenomics

Author:

Takahashi Harumi¹,Ohara Minami¹,Shibata Soichi²,Lee Ming Ta Michael³⁴,Cavallari Larisa H⁵,Nutescu Edith A⁶,Scordo Maria G⁷,Pengo Vittorio⁸,Padrini Roberto⁹,Atsuda Koichiro¹⁰,Matsubara Hajime²,Chen Yuan Tsong⁴,Echizen Hirotoshi¹¹

Affiliation:

1. Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan

2. Department of Pharmacy, Kitasato Institute Hospital, Kitasato University, Tokyo, Japan

3. Geisinger Health System, Danville, PN, USA

4. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

5. Department of Pharmacotherapy & Translational Research & Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA

6. Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA

7. Department of Medical Sciences, Clinical Pharmacology, Uppsala University Hospital, Uppsala, Sweden

8. Department of Cardiothoracic & Vascular Sciences, University of Padova, Padova, Italy

9. Department of Medicine DIMED, University of Padova, Padova, Italy

10. Department of Pharmacy, Kitasato University Hospital, Kanagawa, Japan

11. Department of Pharmacotherapy, Meiji Pharmaceutical University, Tokyo, Japan

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).

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

Link

https://www.futuremedicine.com/doi/pdf/10.2217/pgs-2016-0149

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