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dc.creatorZazo Gómez, Hinojales
dc.creatorLagarejos González, Eduardoes
dc.creatorPrado Velasco, Manuel Augustoes
dc.creatorSánchez Herrero, Sergioes
dc.creatorSerna Pérez, Jeniferes
dc.creatorRueda Ferreiro, Almudenaes
dc.creatorMartín Suárez, Anaes
dc.creatorCalvo Hernández, María Victoriaes
dc.creatorPérez Blanco, Jonás Samueles
dc.creatorMartínez Lanao, Josées
dc.date.accessioned2023-05-08T07:15:58Z
dc.date.available2023-05-08T07:15:58Z
dc.date.issued2022
dc.identifier.citationZazo Gómez, H., Lagarejos González, E., Prado Velasco, M.A., Sánchez Herrero, S., Serna Pérez, J., Rueda Ferreiro, A.,...,Martínez Lanao, J. (2022). Physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPK. Frontiers in Pharmacology, 13 (977372). https://doi.org/10.3389/fphar.2022.977372.
dc.identifier.issn1663-9812es
dc.identifier.urihttps://hdl.handle.net/11441/145528
dc.description.abstractEach year, infections caused around the 25% of neonatal deaths. Early empirical treatments help to reduce this mortality, although optimized dosing regimens are still lacking. The aims were to develop and validate a gentamicin physiologically-based pharmacokinetic (PBPK) model and then potentially explore dosing regimens in neonates using pharmacokinetic and pharmacodynamic criteria. The PBPK model developed consisted of 2 flowlimited tissues: kidney and other tissues. It has been implemented on a new tool called PhysPK, which allows structure reusability and evolution as predictive engine in Model-Informed Precision Dosing (MIPD). Retrospective pharmacokinetic information based on serum levels data from 47 neonates with gestational age between 32 and 39 weeks and younger than one-week postnatal age were used for model validation. The minimal PBPK model developed adequately described the gentamicin serum concentration-time profile with an average fold error nearly 1. Extended interval gentamicin dosing regimens (6 mg/kg q36h and 6 mg/kg q48h for term and preterm neonates, respectively) showed efficacy higher than 99% with toxicity lower than 10% through Monte Carlo simulation evaluations. The gentamicin minimal PBPK model developed in PhysPK from literature information, and validated in preterm and term neonates, presents adequate predictive performance and could be useful for MIPD strategies in neonates.es
dc.formatapplication/pdfes
dc.format.extent12 p.es
dc.language.isoenges
dc.publisherFrontiers Mediaes
dc.relation.ispartofFrontiers in Pharmacology, 13 (977372).
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectPBPKes
dc.subjectGentamicines
dc.subjectNeonateses
dc.subjectPhysPK softwarees
dc.subjectDosing evaluationes
dc.subjectTDMes
dc.titlePhysiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPKes
dc.typeinfo:eu-repo/semantics/articlees
dcterms.identifierhttps://ror.org/03yxnpp24
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Ingeniería Gráficaes
dc.relation.publisherversionhttps://www.frontiersin.org/articles/10.3389/fphar.2022.977372/fulles
dc.identifier.doi10.3389/fphar.2022.977372es
dc.contributor.groupUniversidad de Sevilla. TIC214: Modelado Multiescala y Tecnologías Emergentes en Bioingenieríaes
dc.journaltitleFrontiers in Pharmacologyes
dc.publication.volumen13es
dc.publication.issue977372es

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