{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T22:29:34Z","timestamp":1778279374354,"version":"3.51.4"},"reference-count":49,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35 ES030443"],"award-info":[{"award-number":["R35 ES030443"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 GM113770"],"award-info":[{"award-number":["T32 GM113770"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016512","name":"Center for Companion Animal Health, University of California, Davis","doi-asserted-by":"publisher","award":["To A.G. for dog PK studies"],"award-info":[{"award-number":["To A.G. for dog PK studies"]}],"id":[{"id":"10.13039\/100016512","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003516","name":"Winn Feline Foundation","doi-asserted-by":"publisher","award":["Every Cat Health Foundation (to A.G. for 1 mg\/kg IV cat studies)"],"award-info":[{"award-number":["Every Cat Health Foundation (to A.G. for 1 mg\/kg IV cat studies)"]}],"id":[{"id":"10.13039\/100003516","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>There are few novel therapeutic options available for companion animals, and medications rely heavily on repurposed drugs developed for other species. Considering the diversity of species and breeds in companion animal medicine, comprehensive PK exposures in the companion animal patient is often lacking. The purpose of this paper was to assess the pharmacokinetics after oral and intravenous dosing in domesticated animal species (dogs, cats, and horses) of a novel soluble epoxide hydrolase inhibitor, EC1728, being developed for the treatment of pain in animals. Results: Intravenous and oral administration revealed that bioavailability was similar for dogs, and horses (42 and 50% F) but lower in mice and cats (34 and 8%, respectively). Additionally, clearance was similar between cats and mice, but &gt;2\u00d7 faster in cats vs. dogs and horses. Efficacy with EC1728 has been demonstrated in mice, dogs, and horses, and despite the rapid clearance of EC1728 in cats, analgesic efficacy was demonstrated in an acute pain model after intravenous but not oral dosing. Conclusion: These results demonstrate that exposures across species can vary, and investigation of therapeutic exposures in target species is needed to provide adequate care that addresses efficacy and avoids toxicity.<\/jats:p>","DOI":"10.3390\/molecules26165034","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T09:58:06Z","timestamp":1629367086000},"page":"5034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Species Differences in Metabolism of Soluble Epoxide Hydrolase Inhibitor, EC1728, Highlight the Importance of Clinically Relevant Screening Mechanisms in Drug Development"],"prefix":"10.3390","volume":"26","author":[{"given":"Cindy B.","family":"McReynolds","sequence":"first","affiliation":[{"name":"UC Davis Comprehensive Cancer Center, Department of Entomology and Nematology, University of California, Davis, Davis, CA 95616, USA"},{"name":"EicOsis, 1930 5th Street, Suite A, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"UC Davis Comprehensive Cancer Center, Department of Entomology and Nematology, University of California, Davis, Davis, CA 95616, USA"},{"name":"EicOsis, 1930 5th Street, Suite A, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7980-9018","authenticated-orcid":false,"given":"Alonso","family":"Guedes","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Morisseau","sequence":"additional","affiliation":[{"name":"UC Davis Comprehensive Cancer Center, Department of Entomology and Nematology, University of California, Davis, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Garcia","sequence":"additional","affiliation":[{"name":"Dechra Development LLC, 1 Monument Sq, Portland, ME 04101, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Knych","sequence":"additional","affiliation":[{"name":"K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA"},{"name":"Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caitlin","family":"Tearney","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Briana","family":"Hamamoto","sequence":"additional","affiliation":[{"name":"K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Hee","family":"Hwang","sequence":"additional","affiliation":[{"name":"UC Davis Comprehensive Cancer Center, Department of Entomology and Nematology, University of California, Davis, Davis, CA 95616, USA"},{"name":"EicOsis, 1930 5th Street, Suite A, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Wagner","sequence":"additional","affiliation":[{"name":"UC Davis Comprehensive Cancer Center, Department of Entomology and Nematology, University of California, Davis, Davis, CA 95616, USA"},{"name":"EicOsis, 1930 5th Street, Suite A, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1408-8317","authenticated-orcid":false,"given":"Bruce D.","family":"Hammock","sequence":"additional","affiliation":[{"name":"UC Davis Comprehensive Cancer Center, Department of Entomology and Nematology, University of California, Davis, Davis, CA 95616, USA"},{"name":"EicOsis, 1930 5th Street, Suite A, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.cvsm.2013.04.001","article-title":"Regulatory framework for the availability and use of animal drugs in the United States","volume":"43","author":"Modric","year":"2013","journal-title":"Vet. 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