| Author |
Watanabe, Kensuke P. Kawata, Minami Ikenaka, Yoshinori Nakayama, Shouta M. M. Ishii, Chihiro Darwish, Wageh Sobhi Saengtienchai, Aksorn Mizukawa, Hazuki Ishizuka, Mayumi |
| Description |
Country affiliation: Japan Author Affiliation: Watanabe KP ( Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.); Kawata M ( Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.); Ikenaka Y ( Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.); Nakayama SM ( Water Research Group, Unit for Environmental Sciences and Management, North-West University, Potchefstroom, South Africa.); Ishii C ( Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.); Darwish WS ( Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.); Saengtienchai A ( Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.); Mizukawa H ( Food Control Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.); Ishizuka M ( Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.) |
| 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. |
| Subject Keyword |
Research Support, Non-u.s. Gov't Rats, Wistar Discipline Environmental Health Discipline Toxicology Male Blood Journal Article Discipline Chemistry Biological Assay Female Feces Half-life Drug Resistance Warfarin Administration, Oral Metabolism, Inborn Errors Metabolome Birds Metabolism Cytochrome P-450 Enzyme System Chemistry Animals Chickens Kinetics Enzymology Pharmacokinetics Microsomes, Liver Methods Analogs & Derivatives |
