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dc.contributor.authorWatanabe, Kensuke P.
dc.contributor.authorIkenaka, Yoshinori
dc.contributor.authorKawata, Minami
dc.contributor.authorNakayama, Shouta M.M.
dc.contributor.authorIshii, Chihiro
dc.date.accessioned2016-09-08T09:38:08Z
dc.date.available2016-09-08T09:38:08Z
dc.date.issued2015
dc.identifier.citationWatanabe, K.P. et al. 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. Environmental toxicology and chemistry, 34(10):2328-2334. [http://dx.doi.org/10.1002/etc.3062]en_US
dc.identifier.issn0730-7268
dc.identifier.issn1552-8618 (Online)
dc.identifier.urihttp://hdl.handle.net/10394/18581
dc.identifier.urihttp://dx.doi.org/10.1002/etc.3062
dc.identifier.urihttp://onlinelibrary.wiley.com/doi/10.1002/etc.3062/full
dc.description.abstractCoumarin-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 sensitivityen_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.subjectCytochrome P450en_US
dc.subjectavianen_US
dc.subjectspecies differenceen_US
dc.subjectwarfarinen_US
dc.subjectpharmacokineticsen_US
dc.titleCytochrome 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 chickenen_US
dc.typeArticleen_US
dc.contributor.researchID27878368 - Ikenaka, Yoshinori


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