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To help develop appropriate pain management practices and to develop a quantitative model for predicting methadone dosimetry, a flow\u2010limited multiroute physiologically based pharmacokinetic (PBPK) model for methadone in dogs constructed with Berkeley Madonna\u2122 was developed. The model accounts for intravenous (IV), subcutaneous (SC), and oral administrations, and compartmentalizes the body into different components. This model was calibrated from plasma pharmacokinetic data after IV administration of methadone in Beagles and Greyhounds. The calibrated model was evaluated with independent data in both breeds of dogs. One advantage of this model is that most physiological parameter values for Greyhounds were taken directly from the original literature. The developed model simulates available pharmacokinetic data for plasma concentrations well for both breeds. After conducting regression analysis, all simulated datasets produced an<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0&gt;\u00a00.80 when compared to the measured plasma concentrations. Comparative analysis of the dosimetry of methadone between the breeds suggested that Greyhounds had ~50% lower 24\u2010hr area under the curve (AUC) of plasma or brain concentrations than in Beagles. Furthermore, population analysis was conducted with this study. This model can be used to predict methadone concentrations in multiple dog breeds using breed\u2010specific parameters.<\/jats:p>","DOI":"10.1111\/jvp.12676","type":"journal-article","created":{"date-parts":[[2018,6,20]],"date-time":"2018-06-20T10:58:57Z","timestamp":1529492337000},"page":"670-683","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The construction and application of a population physiologically based pharmacokinetic model for methadone in Beagles and Greyhounds"],"prefix":"10.1111","volume":"41","author":[{"given":"Trevor","family":"Elwell\u2010Cuddy","sequence":"first","affiliation":[{"name":"Institute of Computational Comparative Medicine (ICCM) Department of Anatomy and Physiology College of Veterinary Medicine Kansas State University Manhattan Kansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Computational Comparative Medicine (ICCM) Department of Anatomy and Physiology College of Veterinary Medicine Kansas State University Manhattan Kansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4037-3472","authenticated-orcid":false,"given":"Butch","family":"KuKanich","sequence":"additional","affiliation":[{"name":"Institute of Computational Comparative Medicine (ICCM) Department of Anatomy and Physiology College of Veterinary Medicine Kansas State University Manhattan Kansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8731-8366","authenticated-orcid":false,"given":"Zhoumeng","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Computational Comparative Medicine (ICCM) Department of Anatomy and Physiology College of Veterinary Medicine Kansas State University Manhattan Kansas"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,6,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1982.217"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(87)90281-X"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/074823379701300401"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40291-015-0137-4"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10646-016-1672-4"},{"key":"e_1_2_9_7_1","first-page":"110","volume-title":"Veterinary anaesthesia","author":"Clarke K. 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