{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:08:20Z","timestamp":1790485700621,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T00:00:00Z","timestamp":1587081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["beva.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Equine Veterinary Journal"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Flunixin meglumine (FM) and phenylbutazone (PBZ) are potent anti\u2010inflammatory agents and as such their potential to mask injuries that would otherwise keep a horse from training or racing is concerning. A common practice in racetrack medicine in the USA is to administer the two drugs within close proximity (24\u00a0hours apart) of each other, raising the concern of pharmacokinetic interactions and enhanced anti\u2010inflammatory effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Describe the pharmacokinetics and effects of PBZ on the clearance of FM when administered in close proximity as well as effects on inflammatory mediators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study design<\/jats:title>\n                    <jats:p>Two\u2010way randomised balanced crossover experiment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twelve Thoroughbred exercised horses received 500\u00a0mg FM IV alone or in combination with 2\u00a0g of IV PBZ 24\u00a0hours later. Blood and urine samples were collected prior to and for up to 120\u00a0hours post\u2010drug administration. Whole blood samples were collected at various times and challenged with lipopolysaccharide or calcium ionophore to induce ex vivo synthesis of eicosanoids. Concentrations of FM, PBZ and eicosanoids were measured using LC\u2010MS\/MS and noncompartmental pharmacokinetic analysis performed on concentration data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Flunixin meglumine clearance was significantly increased when horses received PBZ 24\u00a0hours post\u2010administration (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.03). No other differences in pharmacokinetic parameters were noted between groups. Thromboxane B\n                      <jats:sub>2<\/jats:sub>\n                      was significantly suppressed, relative to baseline for 96\u00a0hours post\u2010FM administration. Subsequent administration of PBZ prolonged the suppression. Prostaglandin E2 was decreased for 24\u00a0hours following administration of FM with subsequent administration of PBZ prolonging the suppression until 120\u00a0hours. PGF\n                      <jats:sub>2alpha<\/jats:sub>\n                      concentrations were decreased for up to 168\u00a0hours post\u2010FM administration. FM administration significantly decreased 15\u2010HETE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main limitations<\/jats:title>\n                    <jats:p>Small sample size and lack of a phenylbutazone\u2010only treatment group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Administration of PBZ post\u2010FM administration increased FM clearance. The anti\u2010inflammatory effects of FM appear to be prolonged when PBZ is administered 24\u00a0hours post\u2010administration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/evj.13260","type":"journal-article","created":{"date-parts":[[2020,3,7]],"date-time":"2020-03-07T19:49:16Z","timestamp":1583610556000},"page":"102-116","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Pharmacokinetics and anti\u2010inflammatory effects of flunixin meglumine as a sole agent and in combination with phenylbutazone in exercised Thoroughbred horses"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8676-4970","authenticated-orcid":false,"given":"Heather K.","family":"Knych","sequence":"first","affiliation":[{"name":"K.L. 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Maddy Equine Analytical Pharmacology Laboratory School of Veterinary Medicine University of California Davis CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Seminoff","sequence":"additional","affiliation":[{"name":"K.L. 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