Pharmacodynamics of the Novel Antifungal Agent F901318 for Acute Sinopulmonary Aspergillosis Caused by Aspergillus flavus

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dc.citation.issue7
dc.citation.volumev. 217
dc.contributor.authorNegri, Clara Ezequiel [UNIFESP]
dc.contributor.authorJohnson, Adam
dc.contributor.authorMcEntee, Laura
dc.contributor.authorBox, Helen
dc.contributor.authorWhalley, Sarah
dc.contributor.authorSchwartz, Julie A.
dc.contributor.authorRamos-Martin, V.
dc.contributor.authorLivermore, Joanne
dc.contributor.authorKolamunnage-Dona, Ruwanthi
dc.contributor.authorColombo, Arnaldo Lopes [UNIFESP]
dc.contributor.authorHope, William W.
dc.coverageCary
dc.date.accessioned2020-07-20T16:31:11Z
dc.date.available2020-07-20T16:31:11Z
dc.date.issued2018
dc.description.abstractBackground. Aspergillus flavus is one of the most common agents of invasive aspergillosis and is associated with high mortality. The orotomides are a new class of antifungal agents with a novel mechanism of action. An understanding of the pharmacodynamics (PD) of the lead compound F901318 is required to plan safe and effective regimens for clinical use. Methods. The pharmacokinetics (PK) and PD of F901318 were evaluated by developing new in vitro and in vivo models of invasive fungal sinusitis. Galactomannan was used as a pharmacodynamic endpoint in all models. Mathematical PK-PD models were used to describe dose-exposure-response relationships. Results. F901318 minimum inhibitory concentrations (MICs) ranged from 0.015 to 0.06 mg/L. F901318 induced a concentration-dependent decline in galactomannan. In the in vitro model, a minimum concentration: MIC of 10 resulted in suppression of galactomannanen
dc.description.abstracthowever, values of approximately 10 and 9-19 when assessed by survival of mice or the decline in galactomannan, respectively, were equivalent or exceeded the effect induced by posaconazole. There was histological clearance of lung tissue that was consistent with the effects of F901318 on galactomannan. Conclusions. F901318 is a potential new agent for the treatment of invasive infections caused by A flavus with PDs that are comparable with other first-line triazole agents.en
dc.description.affiliationUniv Fed Sao Paulo, Escola Paulista Med, Disciplina Infectol, Lab Especial Micol, Sao Paulo, Brazil
dc.description.affiliationUniv Liverpool, Antimicrobial Pharmacodynam & Therapeut, Liverpool, Merseyside, England
dc.description.affiliationCharles River Labs, Davis, CA USA
dc.description.affiliationUniv Liverpool, Inst Translat Med, Dept Biostat, Liverpool, Merseyside, England
dc.description.affiliationUnifespUniv Fed Sao Paulo, Escola Paulista Med, Disciplina Infectol, Lab Especial Micol, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipF2G Ltd.
dc.description.sponsorshipNational Institute of Health Research Clinician Scientist Award
dc.description.sponsorshipCAPES PROEX
dc.description.sponsorshipCAPES-PDSE
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil
dc.description.sponsorshipIDNIH-RCS: CS/08/08
dc.description.sponsorshipIDCAPES: 99999.008426/2014-07
dc.description.sponsorshipIDCNPq: 307510/2015-8
dc.format.extent1118-1127
dc.identifierhttp://dx.doi.org/10.1093/infdis/jix479
dc.identifier.citationJournal Of Infectious Diseases. Cary, v. 217, n. 7, p. 1118-1127, 2018.
dc.identifier.doi10.1093/infdis/jix479
dc.identifier.fileWOS000427845800014.pdf
dc.identifier.issn0022-1899
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55775
dc.identifier.wosWOS:000427845800014
dc.language.isoeng
dc.publisherOxford Univ Press Inc
dc.relation.ispartofJournal Of Infectious Diseases
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectAspergillus flavusen
dc.subjectin vivoen
dc.subjectorotomidesen
dc.subjectpharmacodynamicsen
dc.subjectpharmacokineticsen
dc.titlePharmacodynamics of the Novel Antifungal Agent F901318 for Acute Sinopulmonary Aspergillosis Caused by Aspergillus flavusen
dc.typeinfo:eu-repo/semantics/article
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