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A Population Pharmacokinetic Modeling Approach to Determine the Efficacy of Intravenous Amikacin in Children with Cystic Fibrosis

dc.rights.licenseopenen_US
dc.contributor.authorWOILLARD, J. B.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBOUCHET, Stephane
hal.structure.identifierCentre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
dc.contributor.authorFAYON, Michael
dc.contributor.authorMARQUET, P.
dc.contributor.authorMONCHAUD, C.
hal.structure.identifierCentre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
dc.contributor.authorBUI, Stéphanie
dc.date.accessioned2021-03-15T15:39:01Z
dc.date.available2021-03-15T15:39:01Z
dc.date.issued2020-12-17
dc.identifier.issn0163-4356en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/26668
dc.description.abstractEnBACKGROUND: In children with cystic fibrosis (CF), the currently recommended amikacin dose ranges between 30-35 mg/kg/day; however, data supporting this dosing efficacy is lacking. Herein, the objectives were to develop a non-parametric pharmacokinetic population model (POPPK) for amikacin in children with CF and investigate the efficacy and toxicity at different dose rates for distinct minimum inhibitory concentration (MIC) clinical breakpoints using Monte Carlo simulations. METHODS: Data from 94 children with CF (613 serum concentrations) from the Bordeaux University Hospital’s CF-centre (CRCM) were analyzed. After determination of POPPK parameters and associated influent covariates in Pmetrics, 1000 Monte Carlo simulations were performed for 7 different dose rates between 30 and 60 mg/kg/day, to predict the probability of obtaining peak serum amikacin ≥10 × MIC and trough level ≤ 2.5 mg/L, for MIC values between 1 and 16 mg/L. RESULTS: The median[min-max] age and weight were 10[0.3-17] years and 29[6-71] kg, respectively, with only 2 children under 1 year of age. Body weight and creatinine clearance significantly impacted the amikacin volume of distribution and clearance. The mean relative bias/root mean squared error (RMSE) between observed and individual predicted concentrations was -0.68%/8.1%. Monte Carlo simulations showed that for sensitive bacteria with MICs≤4, 30 mg/kg/day was most appropriate for a 100% success rate; for bacteria with MICs≥8 [e.g. Pseudomonas aeruginosa (MICamikacin=8)], a dose of at least 40 mg/kg/day allowed a high success probability (90%), with a trough level below 2.5 mg/L. CONCLUSIONS: For intermediate pathogens, a dose of at least 40 mg/kg/day can improve efficacy, with an acceptable calculated residual trough level in cases of normal or hyperfiltration. As amikacin undergoes renal clearance, which is immature until one year of age, dosing recommendations for this age group may be markedly high, warranting cautious interpretation.
dc.language.isoENen_US
dc.title.enA Population Pharmacokinetic Modeling Approach to Determine the Efficacy of Intravenous Amikacin in Children with Cystic Fibrosis
dc.title.alternativeTher Drug Moniten_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1097/ftd.0000000000000855en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed33346630en_US
bordeaux.journalTherapeutic Drug Monitoringen_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamPharmacoEpi-Drugsen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03169814
hal.version1
hal.date.transferred2021-03-15T15:39:04Z
hal.exporttrue
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