{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T11:40:31Z","timestamp":1785498031005,"version":"3.56.0"},"reference-count":24,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MiraVista Diagnostics","award":["V2024-101"],"award-info":[{"award-number":["V2024-101"]}]},{"DOI":"10.13039\/100009227","name":"Iowa State University","doi-asserted-by":"publisher","award":["2023 VCS Research Incentive Grant"],"award-info":[{"award-number":["2023 VCS Research Incentive Grant"]}],"id":[{"id":"10.13039\/100009227","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009227","name":"Iowa State University","doi-asserted-by":"publisher","award":["FY23 CVM Seed Grant"],"award-info":[{"award-number":["FY23 CVM Seed Grant"]}],"id":[{"id":"10.13039\/100009227","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Invasive fungal infections (IFIs) are growing in importance in veterinary and human medicine. IFIs such as aspergillosis, blastomycosis, coccidioidomycosis and histoplasmosis remain challenging to treat in dogs. Isavuconazole is a novel antifungal medication that, when compared to currently used azoles, has an expanded spectrum of antifungal activity Rudramurthy (2011), Pfaller (2013), Spec (2018), has more predictable pharmacokinetics in humans Desai (2016), Cojutti (2021) and may cause fewer side effects such as liver and renal toxicity Maertens (2016), DiPippo (2018). The pharmacokinetic profile and safety of isavuconazole in dogs has not yet been characterized. The purpose of this study was to evaluate the pharmacokinetics of isavuconazole in healthy dogs that received a single dose of the prodrug isavuconazonium sulfate. Using full crossover design, six healthy beagle dogs received isavuconazonium sulfate at a mean (+\/- SD) dose of 20.6 (+\/- 2.8) mg\/kg orally and 21.8 (+\/- 4.2) mg\/kg intravenously. Plasma was collected for batched pharmacokinetic analysis of prodrug and metabolite, isavuconazole, by ultra-high-pressure liquid chromatography tandem mass spectrometry (UHPLC-MS\/MS). The median (Q1-Q3) maximum isavuconazole peak plasma concentration was estimated at 3,876.5 (2,811.0\u20134,800.0) ng\/mL following oral administration, with a median (Q1-Q3) peak level at 1.3 (1.0\u20132.0) hours. Following intravenous administration, the median (Q1-Q3) isavuconazole peak plasma concentration was estimated at 3,221.5 (2,241.5\u20133,609.0) ng\/mL, with a median (Q1-Q3) peak level at 0.4 (0.3\u20130.6) hours. The median (Q1-Q3) half-life of isavuconazole was 9.4 (7.0\u201312.2) hours and 14.0 (8.1\u201321.7) hours for oral and intravenous routes, respectively. One dog received inadvertent subcutaneous drug administration without any apparent adverse effects. Another dog experienced an anaphylactic reaction following accidental rapid drug infusion. No other drug-related adverse events were observed. At dosages used in this study, healthy dogs achieved isavuconazole plasma levels comparable to human therapeutic targets, and when properly administered the drug was well-tolerated.<\/jats:p>","DOI":"10.1371\/journal.pone.0305766","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T17:28:04Z","timestamp":1721150884000},"page":"e0305766","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetics of isavuconazonium sulfate and its active metabolite isavuconazole in healthy dogs"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9421-8478","authenticated-orcid":true,"given":"Erin","family":"McQuinn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Mochel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Borts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S.","family":"Hanzlicek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Allenspach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-S\u00e9bastien","family":"Palerme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"issue":"12","key":"pone.0305766.ref001","doi-asserted-by":"crossref","DOI":"10.3390\/ph14121312","article-title":"Advances in Antifungal Drug Development: An Up-To-Date Mini Review","volume":"14","author":"G Bouz","year":"2021","journal-title":"Pharmaceuticals (Basel)"},{"key":"pone.0305766.ref002","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.fgb.2017.10.008","article-title":"Overview of selected virulence attributes in Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Trichophyton rubrum, and Exophiala dermatitidis","volume":"111","author":"H Boral","year":"2018","journal-title":"Fungal Genet Biol"},{"issue":"6","key":"pone.0305766.ref003","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1111\/jvp.12888","article-title":"Clinical pharmacokinetics and outcomes of oral fluconazole therapy in dogs and cats with naturally occurring fungal disease","volume":"43","author":"K KuKanich","year":"2020","journal-title":"J Vet Pharmacol Ther"},{"issue":"4","key":"pone.0305766.ref004","doi-asserted-by":"crossref","first-page":"195","DOI":"10.5326\/JAAHA-MS-6591","article-title":"Comparison of Compounded, Generic, and Innovator-Formulated Itraconazole in Dogs and Cats","volume":"54","author":"J Renschler","year":"2018","journal-title":"J Am Anim Hosp Assoc"},{"issue":"4","key":"pone.0305766.ref005","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.diagmicrobio.2011.08.006","article-title":"In vitro activity of isavuconazole against 208 Aspergillus flavus isolates in comparison with 7 other antifungal agents: assessment according to the methodology of the European Committee on Antimicrobial Susceptibility Testing","volume":"71","author":"SM Rudramurthy","year":"2011","journal-title":"Diagn Microbiol Infect Dis"},{"issue":"8","key":"pone.0305766.ref006","doi-asserted-by":"crossref","first-page":"2608","DOI":"10.1128\/JCM.00863-13","article-title":"In vitro activities of isavuconazole and comparator antifungal agents tested against a global collection of opportunistic yeasts and molds","volume":"51","author":"MA Pfaller","year":"2013","journal-title":"J Clin 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Cresemba NDA 207500 and 207501 Pharmacology Review July 8, 2014. 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Cresemba NDA 207500 and 207501 approval letter, March 6, 2015. Retrieved February 13, 2022, from https:\/\/www.accessdata.fda.gov\/scripts\/cder\/daf\/index.cfm?event=overview.process&ApplNo=207500."},{"key":"pone.0305766.ref016","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.mmcr.2019.12.013","article-title":"HIV-associated disseminated histoplasmosis successfully treated with isavuconazole consolidation therapy","volume":"27","author":"A Mazzella","year":"2020","journal-title":"Med Mycol Case Rep"},{"issue":"3","key":"pone.0305766.ref017","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.02232-18","article-title":"Isavuconazole in the Treatment of Coccidioidal Meningitis","volume":"63","author":"A Heidari","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"issue":"3","key":"pone.0305766.ref018","doi-asserted-by":"crossref","first-page":"e128","DOI":"10.1097\/INF.0000000000003017","article-title":"Isavuconazole as Salvage Therapy for Refractory Pediatric Coccidioidal Meningitis","volume":"40","author":"F Naeem","year":"2021","journal-title":"Pediatr Infect Dis J"},{"issue":"8","key":"pone.0305766.ref019","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1111\/myc.12778","article-title":"Isavuconazole for treatment of rare invasive fungal diseases","volume":"61","author":"OA Cornely","year":"2018","journal-title":"Mycoses"},{"issue":"7","key":"pone.0305766.ref020","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/S1473-3099(16)00071-2","article-title":"Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis","volume":"16","author":"FM Marty","year":"2016","journal-title":"Lancet Infect Dis"},{"issue":"2","key":"pone.0305766.ref021","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"AB Nair","year":"2016","journal-title":"J Basic Clin Pharm"},{"key":"pone.0305766.ref022","unstructured":"Cresemba (isavuconazonium sulfate) [package insert]. Northbrook, IL: Astellas Pharma US, Inc.; 2021."},{"issue":"1","key":"pone.0305766.ref023","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1128\/AAC.50.1.286-293.2006","article-title":"Multiple-dose pharmacokinetics and safety of the new antifungal triazole BAL4815 after intravenous infusion and oral administration of its prodrug, BAL8557, in healthy volunteers","volume":"50","author":"A Schmitt-Hoffmann","year":"2006","journal-title":"Antimicrob Agents Chemother"},{"issue":"4","key":"pone.0305766.ref024","doi-asserted-by":"crossref","first-page":"733","DOI":"10.4155\/bio.10.30","article-title":"Effective screening approach to select esterase inhibitors used for stabilizing ester-containing prodrugs analyzed by LC-MS\/MS","volume":"2","author":"EN Fung","year":"2010","journal-title":"Bioanalysis"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0305766","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T17:28:23Z","timestamp":1721150903000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0305766"}},"subtitle":[],"editor":[{"given":"Adeel","family":"Sattar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,7,16]]},"references-count":24,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0305766","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,16]]}}}