{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T17:36:24Z","timestamp":1758476184283,"version":"3.38.0"},"reference-count":18,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T00:00:00Z","timestamp":1308268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:p>Dirikolu, L., Karpiesiuk, W., Lehner, A. F., Tobin, T. Toltrazuril sulfone sodium salt: synthesis, analytical detection, and pharmacokinetics in the Horse.<jats:italic>J. vet. Pharmacol. Therap.<\/jats:italic>\u00a0<jats:bold>35<\/jats:bold>, 265\u2013274.<\/jats:p><jats:p>Toltrazuril sulfone (ponazuril) is a triazine\u2010based antiprotozoal agent with clinical application in the treatment of equine protozoal myeloencephalomyelitis (EPM). In this study, we synthesized and determined the bioavailability of a sodium salt formulation of toltrazuril sulfone that can be used for the treatment and prophylaxis of EPM in horses. Toltrazuril sulfone sodium salt was rapidly absorbed, with a mean peak plasma concentration of 2400\u2003\u00b1\u2003169 (SEM) ng\/mL occurring at 8\u2003h after oral\u2010mucosal dosing and was about 56% bioavailable compared with the i.v. administration of toltrazuril sulfone in dimethylsulfoxide (DMSO). The relative bioavailability of toltrazuril sulfone suspended in water compared with toltrazuril sulfone sodium salt was 46%, indicating approximately 54% less oral bioavailability of this compound suspended in water. In this study, we also investigated whether this salt formulation of toltrazuril sulfone can be used as a feed additive formulation without significant reduction in oral bioavailability. Our results indicated that toltrazuril sulfone sodium salt is relatively well absorbed when administered with feed with a mean oral bioavailability of 52%. Based on these data, repeated oral administration of toltrazuril sulfone sodium salt with or without feed will yield effective plasma and cerebrospinal fluid (CSF) concentrations of toltrazuril sulfone for the treatment and prophylaxis of EPM and other protozoal diseases of horses and other species. As such, toltrazuril sulfone sodium salt has the potential to be used as feed additive formulations for both the treatment and prophylaxis of EPM and various other apicomplexan diseases.<\/jats:p>","DOI":"10.1111\/j.1365-2885.2011.01315.x","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T23:21:22Z","timestamp":1308352882000},"page":"265-274","source":"Crossref","is-referenced-by-count":7,"title":["Toltrazuril sulfone sodium salt: synthesis, analytical detection, and pharmacokinetics in the Horse"],"prefix":"10.1111","volume":"35","author":[{"given":"L.","family":"DIRIKOLU","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.","family":"KARPIESIUK","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. F.","family":"LEHNER","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"TOBIN","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,6,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1002\/jps.2600821008","article-title":"Novel formulation strategies for improving oral bioavailability of drugs with poor membrane permeation or presystemic metabolism","volume":"82","author":"Aungst B.J.","year":"1993","journal-title":"Journal of Pharmaceutical Sciences"},{"key":"e_1_2_6_3_1","first-page":"57","volume-title":"Current Concepts in the Pharmaceutical Sciences: Biopharmaceutics","author":"Bates T.R.","year":"1970"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/019262339502300203"},{"volume-title":"Eight International Conference on Equine Infectious Disease","year":"1998","author":"Bentz B.G.","key":"e_1_2_6_5_1"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2885.1999.00232.x"},{"key":"e_1_2_6_7_1","first-page":"52","article-title":"New therapeutic approaches to equine protozoal myelo\u2010encephalitis: pharmacokinetics of diclazuril sodium salts in the horse","volume":"7","author":"Dirikolu L.","year":"2006","journal-title":"Veterinary Therapeutics"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2885.2008.01053.x"},{"key":"e_1_2_6_9_1","first-page":"125","article-title":"Cerebrospinal fluid and blood concentrations of Toltrazuril 5% suspension in the Horse after oral dosing","volume":"1","author":"Furr M.","year":"2000","journal-title":"Veterinary Therapeutics"},{"key":"e_1_2_6_10_1","first-page":"215","article-title":"Efficacy of ponazuril 15% oral paste as a treatment for equine protozoal myeloencephalitis","volume":"2","author":"Furr M.","year":"2001","journal-title":"Veterinary Therapeutics"},{"volume-title":"Pharmacokinetics","year":"1975","author":"Gibaldi M.","key":"e_1_2_6_11_1"},{"key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1201\/b14095","volume-title":"Pharmacokinetics","author":"Gibaldi M.","year":"1982"},{"key":"e_1_2_6_13_1","first-page":"128","volume-title":"Absorption and Distribution of Drugs","author":"Gorringe J.A.L.","year":"1964"},{"key":"e_1_2_6_14_1","unstructured":"Granstrom D.E.. 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