{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:33:01Z","timestamp":1770816781924,"version":"3.50.1"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Vet Res"],"abstract":"<jats:title>Abstract\n<\/jats:title><jats:sec>\n                <jats:title>Background\n<\/jats:title>\n                <jats:p>Intra-articular corticosteroids, such as isoflupredone acetate, are commonly used in the treatment of joint inflammation, especially in performance horses. Following administration in a non-inflamed joints blood concentrations of isoflupredone were low and detectable for only a short period of time post-administration compared to synovial fluid concentrations. For some drugs, inflammation can affect pharmacokinetics, therefore, the goal of the current study was to describe the pharmacokinetics of isoflupredone acetate following intra-articular administration using a model of acute synovitis. Secondarily, pharmacodynamic effects, including effects on joint circumference, joint flexion, and lameness following intra-articular administration of isoflupredone acetate in the experimental model were described.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Sixteen horses received a single intra-articular dose of 8\u00a0mg of isoflupredone acetate or saline 12\u00a0h post-administration of lipopolysaccharide. Blood and urine samples were collected up to 72\u00a0h and synovial fluid for 28\u00a0days post-administration, drug concentrations determined by liquid chromatography- mass spectrometry and pharmacokinetic analysis performed. Joint circumference, maximum angle of pain free joint flexion and lameness were evaluated prior to and post-treatment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The maximum isoflupredone plasma concentration was 2.45\u2009\u00b1\u20090.61\u00a0ng\/mL at 2.5\u2009\u00b1\u20090.75\u00a0h and concentrations were less than the limit of quantitation by 72\u00a0h. Isoflupredone was below detectable concentrations in urine by 72\u00a0h post-administration in all horses and no longer detectable in synovial fluid by 96\u00a0h post-administration. Joint circumference was significantly decreased in the isoflupredone treatment group compared to the saline group at 24 and 48\u00a0h post drug administration<jats:bold>.<\/jats:bold> Pain free joint flexion was significantly different between the saline and isoflupredone treatment groups on day 4 post-treatment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Synovial fluid concentrations and maximum plasma concentrations of isoflupredone differed slightly between the current study and a previous one describing administration into a non-inflamed joint, however, the detection time of isoflupredone in blood was comparable. Effects of isoflupredone on joint circumference and degree of pain free joint flexion suggest a short duration of effect with respect to alleviation of lipopolysaccharide induced synovitis, however, results of this study support future studies of the anti-inflammatory effects of intra-articular isoflupredone acetate.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12917-022-03537-5","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T05:03:46Z","timestamp":1670907826000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pharmacokinetics and pharmacodynamics of intra-articular isoflupredone following administration to horses with lipopolysaccharide-induced synovitis"],"prefix":"10.1186","volume":"18","author":[{"given":"Heather K.","family":"Knych","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Weiner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel S.","family":"McKemie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"3537_CR1","doi-asserted-by":"publisher","unstructured":"Knych HK, Harrison LM, White A, Mckemie DS. Disposition of isoflupredone acetate in plasma, urine and synovial fluid following intra-articular administration to exercised Thoroughbred horses. Drug Test Anal. 2016;8(1). https:\/\/doi.org\/10.1002\/dta.1834.","DOI":"10.1002\/dta.1834"},{"key":"3537_CR2","unstructured":"Cheville N. Introduction to Veterinary Pathology. 2nd ed. Ames, IA: Iowa University Press;\u00a01999. p.\u00a0105\u201334."},{"issue":"6","key":"3537_CR3","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1111\/j.2042-3306.1994.tb04056.x","volume":"26","author":"JL Palmer","year":"1994","unstructured":"Palmer JL, Bertone AL. Experimentally-induced synovitis as a model for acute synovitis in the horse. Equine Vet J. 1994;26(6):492\u20135.","journal-title":"Equine Vet J."},{"issue":"2","key":"3537_CR4","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1111\/j.1467-2995.2009.00521.x","volume":"37","author":"C Lindegaard","year":"2010","unstructured":"Lindegaard C, Thomsen MH, Larsen S, Andersen PH. 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Pharmacokinetics of triamcinolone acetonide following intramuscular and intra-articular administration to exercised Thoroughbred horses. Equine Vet J. 2013;45(6):715\u201320.\u00a0https:\/\/doi.org\/10.1111\/evj.12059.","DOI":"10.1111\/evj.12059"},{"issue":"2","key":"3537_CR10","first-page":"107","volume":"77","author":"EC Firth","year":"1987","unstructured":"Firth EC, Wensing T, Seuren F. An induced synovitis disease model in ponies. Cornell Vet. 1987;77(2):107\u201318.","journal-title":"Cornell Vet."},{"issue":"2","key":"3537_CR11","doi-asserted-by":"publisher","first-page":"R35","DOI":"10.1186\/ar2640","volume":"11","author":"JC de Grauw","year":"2009","unstructured":"de Grauw JC, van de Lest CH, van Weeren PR. Inflammatory mediators and cartilage biomarkers in synovial fluid after a single inflammatory insult: a longitudinal experimental study. 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Lippincott Williams & Wilkins; 2002:183."}],"container-title":["BMC Veterinary Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-022-03537-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12917-022-03537-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-022-03537-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T22:09:57Z","timestamp":1671228597000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcvetres.biomedcentral.com\/articles\/10.1186\/s12917-022-03537-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,13]]},"references-count":13,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["3537"],"URL":"https:\/\/doi.org\/10.1186\/s12917-022-03537-5","relation":{},"ISSN":["1746-6148"],"issn-type":[{"value":"1746-6148","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,13]]},"assertion":[{"value":"9 September 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 December 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The animal study was reviewed and approved by the University of California Davis Animal Care and Use Committee and according to ARRIVE guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"None of the other authors have any competing interests or declarations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"436"}}