{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:23:21Z","timestamp":1787837001444,"version":"build-2784847793"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Pharm &amp; Therapeutics"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Canine demodicosis is an inflammatory skin disease caused by\n                    <jats:italic>Demodex canis<\/jats:italic>\n                    mites. While newer isoxazoline classes currently represent the standard of care where licensed and available, prolonged ivermectin treatment remains an effective and cost\u2010effective alternative under specific socioeconomic contexts or clinical challenges associated with specific presentations, such as refractory pododemodicosis. Prolonged ivermectin treatment remains the primary choice, especially in resource\u2010limited settings and certain disease presentations. The aim was to characterize the pharmacokinetics of ivermectin following the reference multi\u2010dose regimen in both healthy (simulated based on a single dose) and demodicosis\u2010infested dogs, and to correlate systemic ivermectin exposure with clinical efficacy. Six healthy dogs received a single oral dose of ivermectin (0.5\u2009mg\/kg), and their profiles were extrapolated to a 56\u2010day regimen, while six demodicosis\u2010infested dogs were treated for 56\u2009days at the same dose rate. MDR1 genotyping was performed in infested dogs prior to treatment. Plasma ivermectin concentrations were quantified by HPLC. After 56\u2009days, trough plasma concentration (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>min<\/jats:sub>\n                    ) values increased 3.48\u2010fold, consistent with\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    increments (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&gt;\u20090.05). Comparative concentration ratios were 2.04 in healthy and 2.56 in infested dogs, without statistical differences (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&gt;\u20090.05). Plasma concentration\u2010time curves showed similar profiles, with comparable\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>0\u201024<\/jats:sub>\n                    values (3231 vs. 3074\u2009ng\u00b7h\/mL). The same trend was observed when ivermectin accumulated after long\u2010term exposure (AUC\n                    <jats:sub>0\u201056<\/jats:sub>\n                    ) (315,476 vs. 294,442). Skin scrapings confirmed mite clearance in treated dogs by Day 56. These findings suggest that prolonged ivermectin administration is safe and effective for treating canine demodicosis.\n                  <\/jats:p>","DOI":"10.1111\/jvp.70102","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:06:43Z","timestamp":1787836003000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics and Efficacy Assessment of Long\u2010Term Ivermectin Treatment in Canine Demodicosis: Drug Disposition and Clinical Outcomes Relationship"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0204-9639","authenticated-orcid":false,"given":"S.","family":"Mart\u00ednez","sequence":"first","affiliation":[{"name":"Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Facultad de Ciencias Veterinarias (FCV) Grupo de Investigaci\u00f3n en Medicina Veterinaria Traslacional (MEVET)  Tandil, Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. J.","family":"Del Sole","sequence":"additional","affiliation":[{"name":"Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Facultad de Ciencias Veterinarias (FCV) Grupo de Investigaci\u00f3n en Medicina Veterinaria Traslacional (MEVET)  Tandil, Buenos Aires Argentina"},{"name":"Centro de Investigaci\u00f3n Veterinaria de Tandil (CIVETAN), UNCPBA \u2010 Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET) \u2010 Comisi\u00f3n de Investigaciones Cient\u00edficas de la Provincia de Buenos Aires (CICPBA)  Tandil, Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6786-8694","authenticated-orcid":false,"given":"L.","family":"Mat\u00e9","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Veterinaria de Tandil (CIVETAN), UNCPBA \u2010 Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET) \u2010 Comisi\u00f3n de Investigaciones Cient\u00edficas de la Provincia de Buenos Aires (CICPBA)  Tandil, Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9598-6786","authenticated-orcid":false,"given":"S.","family":"S\u00e1nchez Bruni","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Veterinaria de Tandil (CIVETAN), UNCPBA \u2010 Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET) \u2010 Comisi\u00f3n de Investigaciones Cient\u00edficas de la Provincia de Buenos Aires (CICPBA)  Tandil, Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Lifschitz","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Veterinaria de Tandil (CIVETAN), UNCPBA \u2010 Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET) \u2010 Comisi\u00f3n de Investigaciones Cient\u00edficas de la Provincia de Buenos Aires (CICPBA)  Tandil, Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ballent","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Veterinaria de Tandil (CIVETAN), UNCPBA \u2010 Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET) \u2010 Comisi\u00f3n de Investigaciones Cient\u00edficas de la Provincia de Buenos Aires (CICPBA)  Tandil, Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"115","article-title":"Predictive Modeling and Simulation Tools in Veterinary Pharmacology: A Review of Dosage Optimization","volume":"47","author":"Albarellos G.","year":"2024","journal-title":"Journal of Veterinary Pharmacology and Therapeutics"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.ejphar.2014.06.052","article-title":"Ivermectin Exposure Leads to Up\u2010Regulation of Detoxification Genes In\u00a0Vitro and In\u00a0Vivo in Mice","volume":"740","author":"Alb\u00e9rich M.","year":"2014","journal-title":"European Journal of Pharmacology"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1002\/bdd.2510110603","article-title":"MODFIT: A Pharmacokinetics Computer Program","volume":"11","author":"Allen G. 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