{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T14:19:51Z","timestamp":1785766791802,"version":"3.56.0"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T00:00:00Z","timestamp":1588896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Veterinary Ophthalmology"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To clarify the detailed pharmacokinetics (PK) of orally administered voriconazole in tear fluid (TF) of horses for evaluating the efficacy of voriconazole secreted into TF against equine keratomycosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Animals studied<\/jats:title><jats:p>Five healthy Thoroughbred horses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedures<\/jats:title><jats:p>Voriconazole was administrated through a nasogastric tube to each horse at a single dose of 4.0\u00a0mg\/kg. TF and blood samples were collected before and periodically throughout the 24\u00a0hours after administration. Voriconazole concentrations in plasma and TF samples were analyzed using liquid chromatography\u2010electrospray tandem\u2010mass spectrometry. The predicted voriconazole concentration in both samples following multiple dosing every 24\u00a0hours was simulated by the superposition principle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mean maximum voriconazole concentrations in plasma and TF were 3.3\u00a0\u03bcg\/mL at 1.5\u00a0h and 1.9\u00a0\u03bcg\/mL at 1.6\u00a0h, respectively. Mean half\u2010life in both samples were 16.4 and 25.2\u00a0h, respectively. The ratio of predicted AUC<jats:sub>0\u201324<\/jats:sub>at steady state in TF (51.3\u00a0\u03bcg\u2219h\/mL) to previously published minimum inhibitory concentration (MIC) of<jats:italic>Aspergillus<\/jats:italic>and<jats:italic>Fusarium<\/jats:italic>species was &gt;100 and 25.7, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrated the detailed single\u2010dose PK of voriconazole in TF after oral administration and simulated the predicted concentration curves in a multiple oral dosing. Based on the analyses of PK\u2010PD, the simulation results indicated that repeated oral administration of voriconazole at 4.0\u00a0mg\/kg\/d achieves the ratio of AUC to MIC associated with treatment efficacy against<jats:italic>Aspergillus<\/jats:italic>species. The detailed PK\u2010PD analyses against pathogenic fungi in TF can be used to provide evidence\u2010based medicine for equine keratomycosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/vop.12764","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T11:52:13Z","timestamp":1588938733000},"page":"640-647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Utility of systemic voriconazole in equine keratomycosis based on pharmacokinetic\u2010pharmacodynamic analysis of tear fluid following oral administration"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9138-6839","authenticated-orcid":false,"given":"Norihisa","family":"Tamura","sequence":"first","affiliation":[{"name":"Miho Training Center Japan Racing Association Racehorse Hospital Ibaraki Japan"},{"name":"Japan Racing Association Equine Research Institute Tochigi 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