• Economou Caleb J P CJP University of Queensland Centre of Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia; ICON Canc, Jiao Xie, Gregory Comadira, Brent Richards, Mandy Tallott, Steven C Wallis, Jenny Ordoñez, Jeffrey Lipman, and Jason A Roberts.
• University of Queensland Centre of Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia; ICON Cancer Foundation, Department of Research, Brisbane, Queensland, Australia.
• Int. J. Antimicrob. Agents. 2019 Sep 1; 54 (3): 351-355.

AbstractThe aim of this study was to describe the population pharmacokinetics of ticarcillin during extended daily diafiltration (EDDf) in critically ill patients with acute kidney injury. Blood samples were collected from critically ill patients prescribed ticarcillin during one to two dosing intervals during which EDDf was performed. Plasma samples were measured using a validated ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Concentration-time data were analysed using a population pharmacokinetics approach with Pmetrics®. A total of 53 blood samples were collected from six critically ill patients (three male). The mean ± standard deviation patient age, weight and body mass index (BMI) was 43 ± 22 years, 88 ± 14 kg and 31 ± 5 kg/m2, respectively. A two-compartment linear model adequately described the data. Median population pharmacokinetic parameter estimates were as follows: clearance in the presence of EDDf (CLEDDf), 6.41 L/h; clearance of EDDf (CLnon-EDDf), 4.97 L/h; volume of distribution of the central compartment (Vc), 56.46 L; intercompartmental clearance from the central to peripheral compartment (kCP), 13.54 L/h; and intercompartmental clearance from the peripheral to central compartment (kPC), 21.93 L/h. This is the first population pharmacokinetic model of ticarcillin in patients receiving EDDf. Large pharmacokinetic variability was found, supporting further investigation of the pharmacokinetics of less-studied β-lactam antibiotics in prolonged intermittent renal replacement therapy.Copyright © 2019 Elsevier Ltd. All rights reserved.

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