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dc.contributor.authorEconomou, Caleb JP
dc.contributor.authorKielstein, Jan T
dc.contributor.authorCzock, David
dc.contributor.authorXie, Jiao
dc.contributor.authorField, Jonathan
dc.contributor.authorRichards, Brent
dc.contributor.authorTallott, Mandy
dc.contributor.authorVisser, Adam
dc.contributor.authorKoenig, Christina
dc.contributor.authorHafer, Carsten
dc.contributor.authorSchmidt, Julius J
dc.contributor.authorLipman, Jeffrey
dc.contributor.authorRoberts, Jason A
dc.date.accessioned2019-12-23T04:37:59Z
dc.date.available2019-12-23T04:37:59Z
dc.date.issued2018
dc.identifier.issn0924-8579
dc.identifier.doi10.1016/j.ijantimicag.2018.03.001
dc.identifier.urihttp://hdl.handle.net/10072/389928
dc.description.abstractObjectives: The aim of this study was to describe the population pharmacokinetics of vancomycin during prolonged intermittent renal replacement therapy (PIRRT) in critically ill patients with acute kidney injury. Methods: Critically ill patients prescribed vancomycin across two sites had blood samples collected during one to three dosing intervals during which PIRRT was performed. Plasma samples were assayed with a validated immunoassay method. Population pharmacokinetic analysis and Monte Carlo simulations were performed using Pmetrics®. The target vancomycin exposures were the area under the concentration–time curve within a 24-h period (AUC0–24)/minimum inhibitory concentration (MIC) ratio of 400 for efficacy and AUC0–24 700 for toxicity. Results: Eleven critically ill patients (seven male) were enrolled and contributed 192 plasma samples. The patient's mean ± standard deviation (SD) age, weight and body mass index (BMI) were 57 ± 13 years, 98 ± 43 kg and 31 ± 9 kg/m2, respectively. A two-compartment linear model adequately described the data. The mean ± SD population pharmacokinetic parameter estimates were PIRRT clearance (CL) 3.47 ± 1.99 L/h, non-PIRRT CL 2.15 ± 2.07 L/h, volume of distribution of the central compartment (Vc) 41.85 ± 24.33 L, distribution rate constant from central to peripheral compartment 5.97 ± 7.93 per h and from peripheral to central compartment 5.29 ± 6.65 per h. Assuming a MIC of 1 mg/L, vancomycin doses of 25 mg/kg per day are suggested to be efficacious, whilst minimising toxic, exposures. Conclusions: This is the first population pharmacokinetic study of vancomycin in patients receiving PIRRT and we observed large pharmacokinetic variability. Empirically, weight-based doses that are appropriate for the duration of PIRRT, should be selected and supplemented with therapeutic drug monitoring.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofpagefrom151
dc.relation.ispartofpageto157
dc.relation.ispartofissue2
dc.relation.ispartofjournalInternational Journal of Antimicrobial Agents
dc.relation.ispartofvolume52
dc.subject.fieldofresearchMedical Microbiology
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences
dc.subject.fieldofresearchcode1108
dc.subject.fieldofresearchcode1115
dc.subject.keywordsAntibiotics
dc.subject.keywordsDosing
dc.subject.keywordsPharmacodynamics
dc.subject.keywordsPharmacokinetics
dc.subject.keywordsProlonged intermittent renal replacement therapy
dc.titlePopulation pharmacokinetics of vancomycin in critically ill patients receiving prolonged intermittent renal replacement therapy
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationEconomou, CJP; Kielstein, JT; Czock, D; Xie, J; Field, J; Richards, B; Tallott, M; Visser, A; Koenig, C; Hafer, C; Schmidt, JJ; Lipman, J; Roberts, JA, Population pharmacokinetics of vancomycin in critically ill patients receiving prolonged intermittent renal replacement therapy, International Journal of Antimicrobial Agents, 2018, 52 (2), pp. 151-157
dcterms.dateAccepted2018-03-02
dcterms.licensehttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.date.updated2019-12-23T04:14:32Z
dc.description.versionAccepted Manuscript (AM)
gro.rights.copyright© 2018 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorRichards, Brent V.


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