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This study documents the pharmacokinetics of S\u2010EPA in dogs and its metabolic pathway. After an oral administration of 15\u2009mg\/kg of S\u2010EPA in dogs, the time to peak concentration was 0.80\u2009h, the mean elimination half\u2010life was 7.3\u2009h, and the absolute bioavailability was 55.8%. Furthermore, we identified S\u2010EPA metabolites in dog plasma and dog liver microsomes by UPLC\u2010Q Exactive Orbitrap HRMS. In dog plasma, we found five metabolites, which came from glucuronidation (M1 and M2), deoxygenation (the amidine M4), glucuronidation of M4 (M3), and desulfonamidation and oxidation of M4 (the carboxylic acid M5). In dog liver microsomes, we identified three major metabolites, namely, the glucuronide conjugate (M6), a mono\u2010oxidation product (M7), and a desulfonamidation and oxidation product (M8). Gut microbiota may cause the differences between <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> oxidation metabolisms. Contrary to EPA, S\u2010EPA did not undergo dealkylation, suggesting that substituting the nitrogen with sulfur affects the metabolism of the adjacent alkyl side chain.<\/jats:p>","DOI":"10.1002\/bmc.5226","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T14:41:05Z","timestamp":1628865665000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetics of S\u2010epacadostat, an indoleamine 2,3\u2010dioxygenase 1 inhibitor, in dog plasma and identification of its metabolites <i>in vivo<\/i> and <i>in vitro<\/i>"],"prefix":"10.1002","volume":"35","author":[{"given":"Yumu","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong Yantai 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