{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:19:57Z","timestamp":1792189197550,"version":"4.4.0"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"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; Sci"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Tolfenamic acid (TA) is a non\u2010steroidal anti\u2010inflammatory drug that is commonly used in veterinary medicine. However, information on its pharmacokinetics in calves, particularly following subcutaneous (SC) administration, is limited. The aim of this study was to characterize the disposition of TA in calves following SC, intramuscular (IM) and intravenous (IV) administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Six calves received TA at a dose of 4\u00a0mg\/kg via each route in a crossover design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TA exhibited route\u2010dependent pharmacokinetics. The terminal elimination half\u2010life increased significantly from IV (6.64\u00a0h) to IM (12.79\u00a0h) and SC (15.11\u00a0h) administration, which is consistent with flip\u2010flop kinetics following extravascular dosing. Following IV administration, the volume of distribution at steady state was moderate (0.67 L\/kg), which suggests extensive plasma protein binding. The time to reach the maximum concentration was similar for the IM and SC routes. However, systemic exposure was markedly lower following SC administration, with peak plasma concentration\n                      <jats:sub>,<\/jats:sub>\n                      area under the curve and bioavailability being approximately half of those observed following IM injection. Plasma concentrations exceeded the EC\n                      <jats:sub>50<\/jats:sub>\n                      values required to inhibit prostaglandin E\n                      <jats:sub>2<\/jats:sub>\n                      and related inflammatory mediators for up to 24 h after IV administration and up to 48 h after IM or SC administration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings demonstrate that SC administration of TA in calves results in prolonged but reduced systemic exposure compared with IM administration. The results support the need for route\u2010specific dosing considerations and provide a basis for further studies on residue depletion and determination of withdrawal period in food\u2010producing calves.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/vms3.71024","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T08:29:21Z","timestamp":1781252961000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetics and Bioavailability of Tolfenamic Acid in Calves: First Evaluation of Subcutaneous Administration"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-2510","authenticated-orcid":false,"given":"Orhan","family":"Corum","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Veterinary Medicine University of Hatay Mustafa Kemal  Hatay T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Mar\u00edn","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Murcia Campus de Espinardo  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Badillo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Murcia Campus de Espinardo  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1567-991X","authenticated-orcid":false,"given":"Duygu","family":"Durna Corum","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Veterinary Medicine University of Hatay Mustafa Kemal  Hatay T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6634-0559","authenticated-orcid":false,"given":"Murat","family":"Yuksel","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Faculty of Veterinary Medicine University of Hatay Mustafa Kemal  Hatay T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9236-0630","authenticated-orcid":false,"given":"Halis","family":"Oguz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Veterinary Medicine University of Selcuk  Konya T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1tima","family":"Mart\u00edn\u2010S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Murcia Campus de Espinardo  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1735-1774","authenticated-orcid":false,"given":"Erdinc","family":"Turk","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Veterinary Medicine University of Hatay Mustafa Kemal  Hatay T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Escudero","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Murcia Campus de Espinardo  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1151-1861","authenticated-orcid":false,"given":"Devran","family":"Coskun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Veterinary Medicine University of Siirt  Siirt T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan Basri","family":"Dingil","sequence":"additional","affiliation":[{"name":"Zirve Veterinary Clinic Iskenderun  Hatay 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":"Department of Pharmacology and Toxicology Faculty of Veterinary Medicine University of Selcuk  Konya T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"e_1_2_12_2_1","first-page":"255","article-title":"Tolfenamic Acid. 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