{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:09:20Z","timestamp":1760234960984,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>The aim of this study was to investigate the safety and pharmacokinetics of trimethoprim-sulphadiazine administered via intravenous regional limb perfusion (IVRLP) into the cephalic vein. According to the hypothesis, the drug could be administered without adverse effects and the synovial concentrations would remain above the minimum inhibitory concentration (MIC) for trimethoprim-sulphadiazine (0.5 and 9.5 \u00b5g\/mL) for 24 h. Ten (n = 10) horses underwent cephalic vein IVRLP with an Esmarch tourniquet applied for 30 min. Four grams (4 g) of trimethoprim-sulphadiazine (TMP-SDZ) were diluted at 0.9% NaCl for a total volume of 100 mL. Synovial fluid and blood samples were obtained immediately before IVRLP and at 0.25, 0.5, 2, 6, 12 and 24 h after the initiation of IVRLP. Trimethoprim and sulphadiazine concentrations were determined using a method based on liquid chromatography\/tandem mass spectrometry. The Cmax (peak drug concentration) values were 36 \u00b1 31.1 and 275.3 \u00b1 214.4 \u00b5g\/mL (TMP and SDZ). The respective tmax (time to reach Cmax) values were 20 \u00b1 7.8 and 26.4 \u00b1 7.2 min. The initial synovial fluid concentrations were high but decreased quickly. No horse had synovial concentrations of trimethoprim-sulphadiazine above the MIC at 12 h. Severe vasculitis and pain shortly after IVRLP, lasting up to one week post-injection, occurred in five out of 10 horses. In conclusion, IVRLP with trimethoprim-sulphadiazine cannot be recommended due to the low concentrations of synovial fluid over time and the frequent severe adverse effects causing pain and discomfort in treated horses. Thus, in cases of septic synovitis with bacteria sensitive to trimethoprim-sulphadiazine, other routes of administration should be considered.<\/jats:p>","DOI":"10.3390\/ani11072085","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T02:28:01Z","timestamp":1626229681000},"page":"2085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing Horses"],"prefix":"10.3390","volume":"11","author":[{"given":"Kajsa","family":"Gustafsson","sequence":"first","affiliation":[{"name":"Department of Large Animal Medicine and Surgery, Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amos J.","family":"Tatz","sequence":"additional","affiliation":[{"name":"Department of Large Animal Medicine and Surgery, Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roee","family":"Dahan","sequence":"additional","affiliation":[{"name":"Department of Large Animal Medicine and Surgery, Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiessam","family":"Abu Ahmad","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University-Hadassah Braun School of Public Health and Community Medicine, Jerusalem 9112102, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malka","family":"Britzi","sequence":"additional","affiliation":[{"name":"National Residue Control Laboratory, Kimron Veterinary Institute, Bet Dagan 50250, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gila A.","family":"Sutton","sequence":"additional","affiliation":[{"name":"Department of Large Animal Medicine and Surgery, Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gal","family":"Kelmer","sequence":"additional","affiliation":[{"name":"Department of Large Animal Medicine and Surgery, Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1136\/vr.i3082","article-title":"Regional Limb Perfusion in Horses","volume":"178","author":"Kelmer","year":"2016","journal-title":"Vet. 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