title: Euthanasia method for mice in rapid time-course pulmonary pharmacokinetic studies.
abstract: To develop a means of euthanasia to support rapid time-course pharmacokinetic studies in mice, we compared retroorbital and intravenous lateral tail vein injection of ketamine-xylazine with regard to preparation time, utility, tissue distribution, and time to onset of euthanasia. Tissue distribution and time to onset of euthanasia did not differ between administration methods. However, retroorbital injection could be performed more rapidly than intravenous injection and was considered to be a technically simple and superior alternative for mouse euthanasia. Retroorbital ketamine-xylazine, CO(2) gas, and intraperitoneal pentobarbital then were compared as euthanasia agents in a rapid time-point pharmacokinetic study. Retroorbital ketamine-xylazine was the most efficient and consistent of the 3 methods, with an average time to death of approximately 5 s after injection. In addition, euthanasia by retroorbital ketamine-xylazine enabled accurate sample collection at closely spaced time points and satisfied established criteria for acceptable euthanasia technique.
authors.affiliation: World Wide Comparative Medicine, Pfizer Global Research and Development, St Louis, Missouri, USA. adam.schoell@pfizer.com
authors.forename: Adam R
authors.initials: AR
authors.lastname: Schoell
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Heyde
authors.forename: Dana E
authors.initials: DE
authors.lastname: Weir
authors.forename: Po-Chang
authors.initials: PC
authors.lastname: Chiang
authors.forename: Yiding
authors.initials: Y
authors.lastname: Hu
authors.forename: David K
authors.initials: DK
authors.lastname: Tung
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000494:pharmacology; D037901:Euthanasia, Animal / Q000379:methods*; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D051379:Mice; D010424:Pentobarbital / Q000008:administration & dosage / Q000494:pharmacology; D010599:Pharmacokinetics; D013997:Time Factors; D014991:Xylazine / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D002245:Carbon Dioxide; D014991:Xylazine; D007649:Ketamine; D010424:Pentobarbital