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In this study, the pharmacokinetics, efficacy and toxicology of fluralaner were investigated in <jats:italic>Mus musculus<\/jats:italic> and <jats:italic>Peromyscus leucopus<\/jats:italic> mice, the main reservoir of <jats:italic>B<\/jats:italic>. <jats:italic>burgdorferi<\/jats:italic> in North America. Fluralaner showed rapid distribution and elimination, leading to fast plasma concentration (C<jats:sub>p<\/jats:sub>) depletion in the first hours after administration followed by a slow elimination rate for several weeks, resulting in a long terminal half-life. Efficacy fell below 100% while C<jats:sub>p<\/jats:sub> (\u00b1\u2009standard deviation) decreased from 196\u2009\u00b1\u200954 to 119\u2009\u00b1\u200962\u00a0ng\/mL. These experimental results were then used in simulations of fluralaner treatment for a duration equivalent to the active period of <jats:italic>Ixodes scapularis<\/jats:italic> larvae and nymphs. Simulations showed that doses as low as 10\u00a0mg\/kg have the potential to protect <jats:italic>P<\/jats:italic>. <jats:italic>leucopus<\/jats:italic> against infestation for a full <jats:italic>I<\/jats:italic>. <jats:italic>scapularis<\/jats:italic> active season if administered at least once every 7\u00a0days. This study shows that investigating the pharmacology of candidate acaricides in combination with pharmacokinetic simulations can provide important information to support the development of effective interventions targeting ecological reservoirs of Lyme disease. It therefore represents a critical step that may help surpass limits inherent to the development of these interventions.<\/jats:p>","DOI":"10.1038\/s41598-024-63799-x","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T13:01:45Z","timestamp":1718197305000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacological studies and pharmacokinetic modelling to support the development of interventions targeting ecological reservoirs of Lyme disease"],"prefix":"10.1038","volume":"14","author":[{"given":"J\u00e9r\u00f4me","family":"Pelletier","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Bouchard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9cile","family":"Aenishaenslin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis","family":"Beaudry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas H.","family":"Ogden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick A.","family":"Leighton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Philippe","family":"Rocheleau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"63799_CR1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1603\/ME11138","volume":"49","author":"RJ Eisen","year":"2012","unstructured":"Eisen, R. 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