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dc.contributor.authorLeshinsky, Jana
dc.contributor.authorMcLachlan, Andrew
dc.contributor.authorFoster, David J. R.
dc.contributor.authorNorris, Ross
dc.contributor.authorBarrs, Vanessa R.
dc.date.accessioned2017-09-15T04:52:51Z
dc.date.available2017-09-15T04:52:51Z
dc.date.issued2017
dc.identifier.issn1932-6203
dc.identifier.doi10.1371/journal.pone.0178783
dc.identifier.urihttp://hdl.handle.net/10072/346772
dc.description.abstractCats are the most common mammal to develop invasive fungal rhinosinusitis caused by cryptic species in Aspergillus section Fumigati that are resistant to azoles but susceptible to caspofungin. In this study nonlinear mixed-effects pharmacokinetic modeling and simulation was used to investigate caspofungin pharmacokinetics and explore dosing regimens in cats using caspofungin minimum effective concentrations (MECs). Plasma concentrations in healthy cats were determined using HPLC-MS/MS after administration of a single and seven consecutive daily intravenous doses of 1 mg/kg caspofungin. In the final pharmacokinetic model an optimum maximum concentration (Cmax): MEC ratio of 10–20 was used to guide caspofungin efficacy. Simulations were performed for dosing regimens (doses 0.25–2 mg/kg and 6–72 h dosing intervals) with and without inclusion of a loading dose. Using a 1 mg/kg dose Cmax first dose was 14.8 μg/mL, Cmax at steady state was 19.8 μg/mL, Cmin was 5 μg/mL and Cmax: MEC was >20 in 42.6% of cats after multiple doses. An optimal Cmax: MEC ratio was achieved in caspofungin simulations using 0.75 mg/kg q 24 h or 1 mg/kg q 72h. However, at 1 mg/kg q 72h, Cmin was < MEC (<1 μg/mL) in over 95% of the population. Using a loading dose of 1 mg/kg and a daily dose of 0.75 mg/kg thereafter, the Cmax: MEC was optimal and Cmin was > 2.5 μg/mL for 98% of the population. Based on the modeling data this dosing regimen is likely to achieve target therapeutic concentrations, meet the proposed Cmax: MEC window and provide consistent exposure between doses.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherPublic Library of Sciences
dc.relation.ispartofpagefrome0178783-1
dc.relation.ispartofpagetoe0178783-14
dc.relation.ispartofissue6
dc.relation.ispartofjournalPLoS One
dc.relation.ispartofvolume12
dc.subject.fieldofresearchVeterinary Pharmacology
dc.subject.fieldofresearchcode070710
dc.titlePharmacokinetics of caspofungin acetate to guide optimal dosing in cats
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.description.versionPublished
gro.rights.copyright© 2017 Leshinsky et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
gro.hasfulltextFull Text
gro.griffith.authorNorris, Ross LG.


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