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dc.contributor.authorDhaese, SAM
dc.contributor.authorColin, P
dc.contributor.authorWillems, H
dc.contributor.authorHeffernan, A
dc.contributor.authorGadeyne, B
dc.contributor.authorVan Vooren, S
dc.contributor.authorDepuydt, P
dc.contributor.authorHoste, E
dc.contributor.authorStove, V
dc.contributor.authorVerstraete, AG
dc.contributor.authorLipman, J
dc.contributor.authorRoberts, JA
dc.contributor.authorDe Waele, JJ
dc.date.accessioned2019-11-13T01:14:48Z
dc.date.available2019-11-13T01:14:48Z
dc.date.issued2019
dc.identifier.issn0924-8579
dc.identifier.doi10.1016/j.ijantimicag.2019.08.024
dc.identifier.urihttp://hdl.handle.net/10072/389107
dc.description.abstractThe study aimed to evaluate saturation of piperacillin elimination in critically ill adult patients. Seventeen critically ill adult patients received continuous and intermittent infusion of piperacillin/tazobactam. Piperacillin plasma concentrations (n = 217) were analysed using population pharmacokinetic (PopPK) modelling. Post-hoc simulations were performed to evaluate the type I error rate associated with the study. Unseen data were used to validate the final model. The mean error (ME) and root mean square error (RMSE) were calculated as a measure of bias and imprecision, respectively. A PopPK model with parallel linear and non-linear elimination best fitted the data. The median and 95% confidence interval (CI) for the model parameters drug clearance (CL), volume of central compartment (V), volume of peripheral compartment (Vp) and intercompartmental clearance (Q) were 9 (7.69-11) L/h, 6.18 (4.93-11.2) L, 11.17 (7.26-12) L and 15.61 (12.66-23.8) L/h, respectively. The Michaelis-Menten constant (Km) and the maximum elimination rate for Michaelis-Menten elimination (Vmax) were estimated without population variability in the model to avoid overfitting and inflation of the type I error rate. The population estimates for Km and Vmax were 37.09 mg/L and 353.57 mg/h, respectively. The bias (ME) was -20.8 (95% CI -26.2 to -15.4) mg/L, whilst imprecision (RMSE) was 49.2 (95% CI 41.2-56) mg/L. In conclusion, piperacillin elimination is (partially) saturable. Moreover, the population estimate for Km lies within the therapeutic window and therefore saturation of elimination should be accounted for when defining optimum dosing regimens for piperacillin in critically ill patients.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherElsevier
dc.publisher.placeNetherlands
dc.relation.ispartofjournalInternational Journal of Antimicrobial Agents
dc.subject.fieldofresearchMedical Microbiology
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences
dc.subject.fieldofresearchcode1108
dc.subject.fieldofresearchcode1115
dc.subject.keywordsPharmacokinetics
dc.subject.keywordsPiperacillin
dc.subject.keywordsSaturation
dc.subject.keywordsCritically ill
dc.titleSaturable elimination of piperacillin in critically ill patients: implications for continuous infusion.
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationDhaese, SAM; Colin, P; Willems, H; Heffernan, A; Gadeyne, B; Van Vooren, S; Depuydt, P; Hoste, E; Stove, V; Verstraete, AG; Lipman, J; Roberts, JA; De Waele, JJ, Saturable elimination of piperacillin in critically ill patients: implications for continuous infusion., International Journal of Antimicrobial Agents, 2019
dcterms.dateAccepted2019-08-24
dc.date.updated2019-11-13T00:38:54Z
gro.description.notepublicThis publication has been entered into Griffith Research Online as an Advanced Online Version
gro.hasfulltextNo Full Text
gro.griffith.authorHeffernan, Aaron J.


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