Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/92839
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dc.contributor.authorGaspar, M. C.-
dc.contributor.authorGrégoire, N.-
dc.contributor.authorSousa, João J. S.-
dc.contributor.authorPais, Alberto A. C. C.-
dc.contributor.authorLamarche, I.-
dc.contributor.authorGobin, P.-
dc.contributor.authorOlivier, J.-C.-
dc.contributor.authorMarchand, S.-
dc.contributor.authorCouet, W.-
dc.date.accessioned2021-02-02T10:05:55Z-
dc.date.available2021-02-02T10:05:55Z-
dc.date.issued2016-
dc.identifier.issn09280987pt
dc.identifier.urihttp://hdl.handle.net/10316/92839-
dc.description.abstractA comparative pharmacokinetic study was conducted in rats after intratracheal aerosolization of levofloxacin, as a solution, as immediate-release chitosan microspheres or as sustained-release PLGA microspheres. A pharmacokinetic model was constructed to model levofloxacin concentrations both in plasma and in the lung epithelial lining fluid (ELF). The plasma and ELF experimental concentration profiles versus time were similar for the intravenous and intratracheal levofloxacin solutions and for the intratracheal levofloxacin-loaded chitosan microsphere dry powder, indicating that levofloxacin diffused almost instantaneously through the broncho-alveolar barrier and that the chitosan microspheres released levofloxacin very rapidly, as anticipated from in vitro release studies. The bioavailability for the intratracheal levofloxacin solution and intratracheal chitosan microspheres was estimated to be 98% and 71%, respectively, both with a direct release into the ELF compartment. The ELF-to-unbound plasma AUC ratios were slightly above 2 and may result from an efflux transport. For the intratracheal PLGA microspheres, a high ELF-to-unbound plasma AUC concentration ratio (311) was observed and high levofloxacin concentrations were maintained in ELF for at least 72h in consistency with the in vitro release studies. The bioavailability was 92%, with 19% of the dose released immediately (burst release) into the ELF and 73% released slowly into the ELF from a depot compartment, i.e. the PLGA microspheres, according to a Weibull model. These results highlight the benefit of using sustained-release microspheres administered as aerosols to provide and to maintain high pulmonary concentrations of an antibiotic characterized with a high permeability profile through the broncho-alveolar barrier. The sustained-release microsphere dry powder aerosol may therefore provide advantages over solutions or pure drug dry powders for inhalation in terms of treatment efficiency, ease of use and frequency of administration.pt
dc.language.isoengpt
dc.publisherElsevierpt
dc.relationSFRH/BD/80307/2011pt
dc.relationPEst-OE/QUI/UI0313/2014pt
dc.rightsopenAccesspt
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt
dc.subjectChitosan; Levofloxacin; Microsphere; PLGA; Pulmonary delivery; Pulmonary pharmacokinetics; Sustained releasept
dc.subject.meshAdministration, Inhalationpt
dc.subject.meshAerosolspt
dc.subject.meshAnimalspt
dc.subject.meshChitosanpt
dc.subject.meshDelayed-Action Preparationspt
dc.subject.meshLactic Acidpt
dc.subject.meshMalept
dc.subject.meshMicrospherespt
dc.subject.meshPolyglycolic Acidpt
dc.subject.meshPolylactic Acid-Polyglycolic Acid Copolymerpt
dc.subject.meshRats, Sprague-Dawleypt
dc.subject.meshAnti-Bacterial Agentspt
dc.subject.meshLevofloxacinpt
dc.titlePulmonary pharmacokinetics of levofloxacin in rats after aerosolization of immediate-release chitosan or sustained-release PLGA microspherespt
dc.typearticle-
degois.publication.firstPage184-191pt
degois.publication.lastPage191pt
degois.publication.titleEuropean Journal of Pharmaceutical Sciencespt
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S092809871630313Xpt
dc.peerreviewedyespt
dc.identifier.doi10.1016/j.ejps.2016.08.024pt
degois.publication.volume93pt
dc.date.embargo2016-01-01*
uc.date.periodoEmbargo0pt
item.grantfulltextopen-
item.fulltextCom Texto completo-
item.openairetypearticle-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.languageiso639-1en-
crisitem.author.deptFaculty of Sciences and Technology-
crisitem.author.parentdeptUniversity of Coimbra-
crisitem.author.researchunitCIEPQPF – Chemical Process Engineering and Forest Products Research Centre-
crisitem.author.researchunitCQC - Coimbra Chemistry Centre-
crisitem.author.researchunitCQC - Coimbra Chemistry Centre-
crisitem.author.parentresearchunitFaculty of Sciences and Technology-
crisitem.author.parentresearchunitFaculty of Sciences and Technology-
crisitem.author.parentresearchunitFaculty of Sciences and Technology-
crisitem.author.orcid0000-0002-5584-6324-
crisitem.author.orcid0000-0001-9718-8035-
crisitem.author.orcid0000-0002-6725-6460-
Appears in Collections:FFUC- Artigos em Revistas Internacionais
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