{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T20:34:36Z","timestamp":1785270876615,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,9,25]],"date-time":"2018-09-25T00:00:00Z","timestamp":1537833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Center for Equine Health at the University of California Davis"},{"name":"California Horse Racing Board"}],"content-domain":{"domain":["beva.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Equine Veterinary Journal"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The use of intra\u2010articular (\n                      <jats:styled-content style=\"fixed-case\">IA<\/jats:styled-content>\n                      ) local anaesthetics has proven to be an effective means to treat post\u2010operative pain. The effects of local anaesthetics on equine chondrocytes are mixed with some studies reporting chondrodestruction and others no adverse effects. A liposomal formulation of bupivacaine is used in people and dogs by intra\u2010 and peri\u2010articular administration to provide up to 72\u00a0h of analgesia. The potential uses, side effects including chondrotoxicity, and likelihood of abuse (long\u2010term analgesic effects) has not been evaluated in horses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Describe bupivacaine concentrations following\n                      <jats:styled-content style=\"fixed-case\">IA<\/jats:styled-content>\n                      administration and assess biomarkers as indicators of the effects of liposomal bupivacaine on chondrocytes in\u00a0vivo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study design<\/jats:title>\n                    <jats:p>Parallel design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Sixteen exercised horses received a single\n                      <jats:styled-content style=\"fixed-case\">IA<\/jats:styled-content>\n                      administration of 0.12\u00a0mg\/kg liposomal bupivacaine or 0.9% saline. Blood and urine samples were collected for 96\u00a0h post\u2010drug administration. Six horses treated with bupivacaine and those receiving saline, underwent daily arthrocentesis. Six additional bupivacaine treated horses underwent arthrocentesis at 96\u00a0h. Drug concentrations were measured using\n                      <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\n                      \/\n                      <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\n                      and pharmacokinetic analyses performed. Immunoassays were used to measure markers of collagen degradation (C2C, C12C) and cartilage matrix synthesis (\n                      <jats:styled-content style=\"fixed-case\">CPII<\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\">CS<\/jats:styled-content>\n                      846) in synovial fluid.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The bupivacaine plasma elimination half\u2010life was 17.8\u00a0\u00b1\u00a05.42 and 11.9\u00a0\u00b1\u00a05.17\u00a0h for horses from which synovial fluid was collected daily and at 96\u00a0h respectively. Bupivacaine concentrations in the joint were still detectable at 96\u00a0h. Significant increases in C12C and C2C were noted at 96\u00a0h in horses undergoing arthrocentesis at 96\u00a0h only.\n                      <jats:styled-content style=\"fixed-case\">CPII<\/jats:styled-content>\n                      was increased at 48\u00a0h and\n                      <jats:styled-content style=\"fixed-case\">CS<\/jats:styled-content>\n                      846 at 24 and 48\u00a0h in horses sampled daily.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main limitations<\/jats:title>\n                    <jats:p>Limited number of animals and absence of liposome control group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Sustained concentrations of\n                      <jats:styled-content style=\"fixed-case\">IA<\/jats:styled-content>\n                      bupivacaine suggest viability of this medication as an intra\u2010articular analgesic. Effects on equine chondrocytes need further study.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/evj.13015","type":"journal-article","created":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T02:50:57Z","timestamp":1536115857000},"page":"408-414","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Plasma and synovial fluid concentrations and cartilage toxicity of bupivacaine following intra\u2010articular administration of a liposomal formulation to horses"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8676-4970","authenticated-orcid":false,"given":"H. K.","family":"Knych","sequence":"first","affiliation":[{"name":"K.L. Maddy Equine Analytical Chemistry Laboratory School of Veterinary Medicine, University of California Davis California USA"},{"name":"Department of Veterinary Molecular Biosciences School of Veterinary Medicine, University of California Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. R.","family":"Mama","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences, Colorado State University Fort Collins Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. E.","family":"Moore","sequence":"additional","affiliation":[{"name":"K.L. Maddy Equine Analytical Chemistry Laboratory School of Veterinary Medicine, University of California Davis California USA"},{"name":"Department of Veterinary Molecular Biosciences School of Veterinary Medicine, University of California Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9546-5630","authenticated-orcid":false,"given":"A. E.","family":"Hill","sequence":"additional","affiliation":[{"name":"California Animal Health and Food Safety Laboratory School of Veterinary Medicine, University of California Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. S.","family":"McKEMIE","sequence":"additional","affiliation":[{"name":"K.L. 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