HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
獣医学研究科  >
雑誌発表論文等  >

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

フルテキスト
EnvironToxicolChem34(10)2328.pdf427.24 kBPDF見る/開く
この文献へのリンクには次のURLを使用してください:http://hdl.handle.net/2115/62929

タイトル: 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
著者: Watanabe, Kensuke P. 著作を一覧する
Kawata, Minami 著作を一覧する
Ikenaka, Yoshinori 著作を一覧する
Nakayama, Shouta M. M. 著作を一覧する
Ishii, Chihiro 著作を一覧する
Darwish, Wageh Sobhi 著作を一覧する
Saengtienchai, Aksorn 著作を一覧する
Mizukawa, Hazuki 著作を一覧する
Ishizuka, Mayumi 著作を一覧する
キーワード: Avian
Cytochrome P450
Species difference
Warfarin
Pharmacokinetics
発行日: 2015年10月
出版者: Wiley-Blackwell
誌名: Environmental Toxicology and Chemistry
巻: 34
号: 10
開始ページ: 2328
終了ページ: 2334
出版社 DOI: 10.1002/etc.3062
抄録: 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.
資料タイプ: article (author version)
URI: http://hdl.handle.net/2115/62929
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 石塚 真由美

 

本サイトに関するご意見・お問い合わせは repo at lib.hokudai.ac.jp へお願いします。 - 北海道大学