{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T09:05:01Z","timestamp":1765098301745,"version":"3.37.3"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T00:00:00Z","timestamp":1436832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Purdue University Canine Disease Research Fund"},{"name":"Purdue Comparative Oncology Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Comparative Oncology"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The purpose of this study was to determine the plasma pharmacokinetics (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>) and toxicity of zebularine, an oral cytidine analog with demethylating activity, in dogs. Plasma zebularine concentrations were determined by <jats:styled-content style=\"fixed-case\">HPLC\u2010MS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> following an oral zebularine dose of 8 or 4\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup>. Plasma zebularine clearance was constant. <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>ean maximum concentration (C<jats:sub>max<\/jats:sub>) was 23\u2009\u00b1\u20094.8 and 8.6\u2009\u00b1\u20091.4\u2009\u00b5M following 8 and 4\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup>, respectively. Mean half\u2010life was 5.7\u2009\u00b1\u20090.84 and 7.1\u2009\u00b1\u20092.1 following 8 and 4\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup>, respectively. A single 8\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup> dose was well tolerated. Daily 4\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup> treatment in three laboratory dogs resulted in grade 4 neutropenia (<jats:italic>n<\/jats:italic>\u2009=\u20093), grade 1 anorexia (<jats:italic>n<\/jats:italic>\u2009=\u20092) and grade 1 or 2 dermatologic changes (<jats:italic>n<\/jats:italic>\u2009=\u20092). All adverse events resolved with supportive care. A 4\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup> dose every 21\u2009days was well tolerated. A follow\u2010up dose escalation study is in progress with a lower starting dose.<\/jats:p>","DOI":"10.1111\/vco.12159","type":"journal-article","created":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T16:25:11Z","timestamp":1436891111000},"page":"226-236","source":"Crossref","is-referenced-by-count":9,"title":["Pharmacokinetics and toxicity of the novel oral demethylating agent zebularine in laboratory and tumor bearing dogs"],"prefix":"10.1111","volume":"15","author":[{"given":"C. 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W.","family":"Knapp","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences Purdue University College of Veterinary Medicine  West Lafayette IN USA"},{"name":"Purdue University Center for Cancer Research  West Lafayette IN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,7,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg816"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0320910"},{"key":"e_1_2_7_4_1","unstructured":"Marquez VE. Recent developments of two NCI epigenetic drugs: zebularine and 3\u2010deazaneplanocin\u2010A. 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