{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T07:06:05Z","timestamp":1771052765172,"version":"3.50.1"},"reference-count":131,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":825,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T00:00:00Z","timestamp":1693872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016512","name":"Center for Companion Animal Health, University of California, Davis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016512","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Holliday Neurology Resident Research Grant"},{"DOI":"10.13039\/100016512","name":"Center for Companion Animal Health, University of California, Davis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016512","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cytosine arabinoside (Ara-C) is a nucleoside analog prodrug utilized for immunomodulatory effects mediated by its active metabolite Ara-CTP. Optimal dosing protocols for immunomodulation in dogs have not been defined. Cytarabine ocfosfate (CO) is a lipophilic prodrug of Ara-C that can be administered PO and provides prolonged serum concentrations of Ara-C.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Provide pharmacokinetic data for orally administered CO and determine accumulation and functional consequences of Ara-CTP within peripheral blood leukocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Three healthy female hound dogs and 1 healthy male Beagle.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Prospective study. Dogs received 200\u2009mg\/m2 of CO PO q24h for 7 doses. Serum and cerebrospinal fluid (CSF) CO and Ara-C concentrations were measured by liquid chromatography-tandem mass spectroscopy (LC-MS\/MS). Complete blood counts, flow cytometry, and leukocyte activation assays were done up to 21\u2009days. Incorporation of Ara-CTP within leukocyte DNA was determined by LC-MS\/MS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Maximum serum concentration (Cmax) for Ara-C was 456.1-724.0\u2009ng\/mL (1.88-2.98\u2009\u03bcM) and terminal half-life was 23.3 to 29.4\u2009hours. Cerebrospinal fluid: serum Ara-C ratios ranged from 0.54 to 1.2. Peripheral blood lymphocyte concentrations remained within the reference range, but proliferation rates poststimulation were decreased at 6\u2009days. Incorporation of Ara-CTP was not saturated and remained &amp;gt;25% of peak concentration at 13\u2009days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Clinical Importance<\/jats:title>\n                    <jats:p>Oral CO may produce prolonged serum Ara-C half-lives at concentrations sufficient to induce functional changes in peripheral leukocytes and is associated with prolonged retention of DNA-incorporated Ara-CTP. Application of functional and active metabolite assessment is feasible and may provide more relevant data to determine optimal dosing regimens for Ara-C-based treatments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.16842","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T01:51:12Z","timestamp":1693965072000},"page":"2429-2442","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Oral cytarabine ocfosfate pharmacokinetics and assessment of leukocyte biomarkers in normal dogs"],"prefix":"10.1093","volume":"37","author":[{"given":"Danielle M.","family":"Zwueste","sequence":"first","affiliation":[{"name":"William R. Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California , Davis, California,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen M.","family":"Vernau","sequence":"additional","affiliation":[{"name":"University of California Davis Department of Surgical and Radiological Sciences, , Davis, California,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Vernau","sequence":"additional","affiliation":[{"name":"Microbiology and Immunology, University of California Davis Department of Pathology, , Davis, California,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno H.","family":"Pypendop","sequence":"additional","affiliation":[{"name":"University of California Davis Department of Surgical and Radiological Sciences, , Davis, California,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather K.","family":"Knych","sequence":"additional","affiliation":[{"name":"K.L. Maddy Equine Analytic Chemistry Laboratory, UC Davis , Davis, California,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos A.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"University of California Davis Department of Surgical and Radiological Sciences, , Davis, California,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir","family":"Kol","sequence":"additional","affiliation":[{"name":"Microbiology and Immunology, University of California Davis Department of Pathology, , Davis, California,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Questa","sequence":"additional","affiliation":[{"name":"Microbiology and Immunology, University of California Davis Department of Pathology, , Davis, California,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0037-2619","authenticated-orcid":false,"given":"Peter J.","family":"Dickinson","sequence":"additional","affiliation":[{"name":"University of California Davis Department of Surgical and Radiological Sciences, , Davis, California,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,11,1]]},"reference":[{"key":"2026021401281817100_jvim16842-bib-0001","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3390\/cancers13050966","article-title":"Response and toxicity to cytarabine therapy in leukemia and lymphoma: from dose puzzle to pharmacogenomic biomarkers","volume":"13","author":"di Francia","year":"2021","journal-title":"Cancers 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