{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T14:10:12Z","timestamp":1767363012058,"version":"3.48.0"},"reference-count":98,"publisher":"American Veterinary Medical Association (AVMA)","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":[[2026,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"sc_a1\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine the systemic and CNS distribution of bumped-kinase inhibitors (BKIs) in healthy horses, assess potential side effects, and identify a candidate compound for a clinical trial in equine protozoal myeloencephalitis (EPM) cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sc_a2\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      9 pharmacokinetic (PK) experiments were conducted from March 2021 through November 2024. Bumped-kinase inhibitors 1708, 1748, and 1841 were screened in\n                      <jats:italic>Sarcocystis neurona<\/jats:italic>\n                      growth assays and IV PKs, followed by investigation of a lead BKI compound by single-dose or multiday oral administration. Serial plasma collections were performed to assess systemic distribution, and CNS penetration was determined based on drug concentrations in CSF and nervous tissue. Side effects were monitored by daily physical examinations, CBC, and blood biochemistry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sc_a3\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BKI-1708 was identified as a lead compound based on in vitro inhibition of\n                      <jats:italic>S neurona<\/jats:italic>\n                      growth at low nanomolar concentrations (half-maximum inhibitory concentration, 42 nM) and a lack of side effects. Based on IV and oral PK studies, a single daily dose was sufficient to achieve therapeutic concentrations systemically (average peak concentration of 5 \u03bcM and half-life of 25 hours at steady state). However, BKI-1708 concentrations in CSF and nervous tissue were 25-fold lower than in plasma, suggesting low CNS penetration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sc_a4\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although BKI-1708 did not achieve therapeutic concentrations in the CNS, the systemic PK profile warrants further investigation for use as EPM prophylaxis based on intermittent drug administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sc_a5\">\n                    <jats:title>Clinical Relevance<\/jats:title>\n                    <jats:p>BKI-1708 is a potential compound for EPM prevention and treatment of systemic apicomplexan-related diseases in horses, such as piroplasmosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2460\/ajvr.25.07.0270","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T16:59:34Z","timestamp":1760461174000},"source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic analysis of bumped-kinase inhibitors in horses demonstrates their potential utility for prevention and treatment of equine protozoal myeloencephalitis"],"prefix":"10.2460","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9765-813X","authenticated-orcid":true,"given":"Izabela de Assis","family":"Rocha","sequence":"first","affiliation":[{"name":"Department of Veterinary Science, Martin-Gatton College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenna L.","family":"McPeek","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, Martin-Gatton College of Agriculture, Food and Environment, University of Kentucky, 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