{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:46:53Z","timestamp":1791906413882,"version":"4.3.4"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Veterinary Medicine &amp;amp; Sci"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The purpose of this study was to investigate the pharmacokinetic alterations of flunixin and tolfenamic acid in experimental endotoxemic sheep.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The study was conducted on 12 healthy Awassi sheep. The sheep were divided into two equal groups, tolfenamic acid (\n                      <jats:italic>n<\/jats:italic>\n                      = 6) and flunixin (\n                      <jats:italic>n<\/jats:italic>\n                      = 6), and the study in each group was carried out in two stages. The initial stage involved the intravenous (IV) administration of flunixin and tolfenamic acid to healthy sheep at doses of 2.2\u00a0mg\/kg and 4\u00a0mg\/kg, respectively. In the second stage, sheep were administered LPS (\n                      <jats:italic>E. coli<\/jats:italic>\n                      O55:B5, 10 \u00b5g\/kg) followed by IV administration of tolfenamic acid and flunixin. The analysis of drugs was performed using HPLC\u2010UV, and pharmacokinetic parameters were calculated by non\u2010compartmental analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The t\n                      <jats:sub>1\/2\u028ez<\/jats:sub>\n                      , Cl\n                      <jats:sub>T<\/jats:sub>\n                      , and V\n                      <jats:sub>dss<\/jats:sub>\n                      values were found to be 3.74\u00a0h, 0.17 L\/h\/kg, and 0.54 L\/kg for tolfenamic acid and 3.14\u00a0h, 0.04 L\/h\/kg, and 0.12 L\/kg for flunixin in healthy sheep, respectively. Both drugs showed longer t\n                      <jats:sub>1\/2\u028ez<\/jats:sub>\n                      and MRT\n                      <jats:sub>0\u2010\u221e<\/jats:sub>\n                      , higher AUC\n                      <jats:sub>0\u2010\u221e<\/jats:sub>\n                      , and lower Cl\n                      <jats:sub>T<\/jats:sub>\n                      in endotoxemic sheep compared to healthy sheep. The V\n                      <jats:sub>dss<\/jats:sub>\n                      values of both drugs were similar between healthy sheep and endotoxemic sheep.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The altered pharmacokinetics of flunixin and tolfenamic acid in endotoxemic sheep suggest that dose adjustments and careful therapeutic monitoring are necessary to maintain efficacy and safety.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/vms3.70954","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T18:54:32Z","timestamp":1777056872000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetics of Flunixin and Tolfenamic Acid in Experimental Endotoxemic Awassi Sheep"],"prefix":"10.1002","volume":"12","author":[{"given":"Fulya","family":"Altinok\u2010Yipel","sequence":"first","affiliation":[{"name":"Faculty of Veterinary Medicine Department of Veterinary Internal Medicine Necmettin Erbakan University  Ere\u011fli Konya T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-2510","authenticated-orcid":false,"given":"Orhan","family":"Corum","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine Department of Pharmacology and Toxicology Hatay Mustafa Kemal University  Hatay T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duygu","family":"Durna Corum","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine Department of Pharmacology and Toxicology Hatay Mustafa Kemal University  Hatay T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erdinc","family":"Turk","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine Department of Pharmacology and Toxicology Hatay Mustafa Kemal University  Hatay T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramazan","family":"Yildiz","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine Department of Internal Medicine Burdur Mehmet Akif Ersoy University  Burdur T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9716-0697","authenticated-orcid":false,"given":"Mehmet","family":"Guvenc","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine Department of Physiology Hatay Mustafa Kemal University  Hatay T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3491-5949","authenticated-orcid":false,"given":"Aysun","family":"Ilhan","sequence":"additional","affiliation":[{"name":"Ministry of Agriculture and Forestry Tunceli Provincial Directorate P\u00fcl\u00fcm\u00fcr District Directorate  P\u00fcl\u00fcm\u00fcr T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8674-4873","authenticated-orcid":false,"given":"Kamil","family":"Uney","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine Department of Pharmacology and Toxicology Selcuk University  Konya T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"Anonymous.2025.https:\/\/www.msd\u2010animal\u2010health.co.in\/products\/finadynetm\/(accessed 08 May 2025)."},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smallrumres.2025.107461"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-012-0551-6"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvp.12702"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/vms3.1533"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/vms3.70047"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvp.12849"},{"key":"e_1_2_12_9_1","unstructured":"CVMP.1997. \u201cCommittee for Veterinary Medicinal Products: Tolfenamic Acid Summary Report.EMEA\/MRL\/183\/97\u2010FINAL.\u201d (accessed 08 May 2025).http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Maximum_Residue_Limits_\u2010_Report\/2009\/11\/WC500015620.pdf."},{"key":"e_1_2_12_10_1","unstructured":"Da Silva G. 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