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Cytochrome P450-mediated warfarin metabolic ability is not a critical determinant of warfarin sensitivity in avian species: In vitro assays in several birds and in vivo assays in chicken

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Title: Cytochrome P450-mediated warfarin metabolic ability is not a critical determinant of warfarin sensitivity in avian species: In vitro assays in several birds and in vivo assays in chicken
Authors: Watanabe, Kensuke P. Browse this author
Kawata, Minami Browse this author
Ikenaka, Yoshinori Browse this author →KAKEN DB
Nakayama, Shouta M. M. Browse this author →KAKEN DB
Ishii, Chihiro Browse this author
Darwish, Wageh Sobhi Browse this author
Saengtienchai, Aksorn Browse this author
Mizukawa, Hazuki Browse this author →KAKEN DB
Ishizuka, Mayumi Browse this author →KAKEN DB
Keywords: Avian
Cytochrome P450
Species difference
Warfarin
Pharmacokinetics
Issue Date: Oct-2015
Publisher: Wiley-Blackwell
Journal Title: Environmental Toxicology and Chemistry
Volume: 34
Issue: 10
Start Page: 2328
End Page: 2334
Publisher DOI: 10.1002/etc.3062
PMID: 25959534
Abstract: Coumarin-derivative anticoagulant rodenticides used for rodent control are posing a serious risk to wild bird populations. For warfarin, a classic coumarin derivative, chickens have a high median lethal dose (LD50), whereas mammalian species generally have much lower LD50. Large interspecies differences in sensitivity to warfarin are to be expected. The authors previously reported substantial differences in warfarin metabolism among avian species; however, the actual in vivo pharmacokinetics have yet to be elucidated, even in the chicken. In the present study, the authors sought to provide an in-depth characterization of warfarin metabolism in birds using in vivo and in vitro approaches. A kinetic analysis of warfarin metabolism was performed using liver microsomes of 4 avian species, and the metabolic abilities of the chicken and crow were much higher in comparison with those of the mallard and ostrich. Analysis of in vivo metabolites from chickens showed that excretions predominantly consisted of 4-hydroxywarfarin, which was consistent with the in vitro results. Pharmacokinetic analysis suggested that chickens have an unexpectedly long half-life despite showing high metabolic ability in vitro. The results suggest that the half-life of warfarin in other bird species could be longer than that in the chicken and that warfarin metabolism may not be a critical determinant of species differences with respect to warfarin sensitivity. Environ Toxicol Chem 2015;34:2328-2334. (c) 2015 SETAC
Rights: This is the peer reviewed version of the following article: Watanabe KP, Kawata M, Ikenaka Y, Nakayama SMM, Ishii C, Darwish WS, Saengtienchai A, Mizukawa H, Ishizuka M. 2015. Cytochrome P450-mediated warfarin metabolic ability is not a critical determinant of warfarin sensitivity in avian species: In vitro assays in several birds and in vivo assays in chicken. Environ Toxicol Chem 34:2328-2334, which has been published in final form at http://dx.doi.org/10.1002/etc.3062. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Type: article (author version)
URI: http://hdl.handle.net/2115/62929
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 石塚 真由美

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