{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T13:13:04Z","timestamp":1780060384999,"version":"3.54.0"},"reference-count":58,"publisher":"American Veterinary Medical Association (AVMA)","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"sc_a1\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Osteoarthritis (OA) is a prevalent and debilitating degenerative joint disease in both humans and companion animals, leading to chronic pain and mobility loss. The inflammation has been identified to play a critical role in OA progression. Our prior work revealed that cyclin-dependent kinase 9 acts as a key regulator of early inflammatory gene activation and found an effective inhibitor, flavopiridol. To develop flavopiridol into an effective prevention and treatment of OA, this study focuses on the pharmacokinetics of our flavopiridol formulations upon IA injection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sc_a2\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>12 male 14-week-old Lewis rats (n = 4 per group) received IA administration of flavopiridol in either free form or encapsulated in poly(lactic-co-glycolic acid) microparticles. Blood samples were collected via the saphenous vein at multiple time points. Plasma flavopiridol concentrations were quantified using a validated liquid chromatography\u2013mass spectrometry assay. Pharmacokinetic parameters were determined by noncompartmental analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sc_a3\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Free flavopiridol exhibited a higher peak plasma concentration and a shorter elimination half-life than that of poly(lactic-co-glycolic acid) microparticle encapsulated formulations. In contrast, microparticle formulation provided sustained release of flavopiridol for at least 3 weeks, with a significantly lower mean peak plasma concentration and prolonged elimination half-life.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sc_a4\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Free flavopiridol has a short elimination half-life and limited systemic retention. In contrast, IA administration of microparticle encapsulated inhibitors offers sustained release and prolonged drug exposure at the target site while minimizing systemic side effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sc_a5\">\n                    <jats:title>Clinical Relevance<\/jats:title>\n                    <jats:p>The microparticle-based sustained-release formulation provides a promising means for the prevention and long-term treatment of joint inflammation and OA in both humans and animals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2460\/ajvr.25.10.0380","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T17:07:45Z","timestamp":1772471265000},"source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics of intra-articular delivery of flavopiridol-loaded microparticles reveal sustained effects in Lewis rats"],"prefix":"10.2460","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0438-9693","authenticated-orcid":true,"given":"Yihan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Xiangya Second Hospital, Central South University, Changsha, Hunan Province, China"},{"name":"Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China"},{"name":"Department of Orthopaedic Surgery, School of Medicine, University of California-Davis, Davis, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"issue":"1","key":"B1","series-title":"Arthritis Res Ther","first-page":"57","article-title":"Post-traumatic osteoarthritis following ACL injury","author":"Wang LJ","year":"2020","unstructured":"Wang LJ, Zeng N, Yan ZP, Li JT, Ni GX. Post-traumatic osteoarthritis following ACL injury. Arthritis Res Ther. 2020;22(1):57. doi:10.1186\/s13075-020-02156-5"},{"issue":"15","key":"B2","series-title":"Int J Mol Sci","first-page":"8005","article-title":"Anti-inflammatory therapeutic approaches to prevent or delay post-traumatic osteoarthritis (PTOA) of the knee joint with a focus on sustained delivery approaches","author":"Khella CM","year":"2021","unstructured":"Khella CM, Horvath JM, Asgarian R, Rolauffs B, Hart ML. Anti-inflammatory therapeutic approaches to prevent or delay post-traumatic osteoarthritis (PTOA) of the knee joint with a focus on sustained delivery approaches. Int J Mol Sci. 2021;22(15):8005. doi:10.3390\/ijms22158005"},{"key":"B3","series-title":"Osteoarthritis","first-page":"655","article-title":"Diagnosis and management of lameness in the horse","author":"Caron J","year":"2011","unstructured":"Caron J, Ross M, Dyson S. Diagnosis and management of lameness in the horse. Osteoarthritis. Elsevier Saunders; 2011:655\u2013668."},{"key":"B4","series-title":"Nat Rev Rheumatol","first-page":"92","article-title":"Strategies for the prevention of knee osteoarthritis","author":"Roos EM","year":"2016","unstructured":"Roos EM, Arden NK. Strategies for the prevention of knee osteoarthritis. Nat Rev Rheumatol. 2016;12:92\u2013101. doi:10.1038\/nrrheum.2015.135"},{"key":"B5","series-title":"Mol Imaging","first-page":"1536012117714575","article-title":"Feasibility of Na18F PET\/CT and MRI for noninvasive in vivo quantification of knee pathophysiological bone metabolism in a canine model of post-traumatic osteoarthritis","author":"Menendez MI","year":"2017","unstructured":"Menendez MI, Hettlich B, Wei L, Knopp MV. Feasibility of Na18F PET\/CT and MRI for noninvasive in vivo quantification of knee pathophysiological bone metabolism in a canine model of post-traumatic osteoarthritis. 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