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External Evaluation of Intravenous Vancomycin Population Pharmacokinetics Models in Adults Receiving High-flux Intermittent Hemodialysis
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  • Cheng Ji,
  • Jonathan Garcia,
  • Argem Sabuga,
  • Maurane Ricard,
  • France Dion,
  • Vlad Rosu,
  • Marie-Eve Legris,
  • Amélie Marsot,
  • Van Dong Nguyen
Cheng Ji
McGill University Health Centre
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Jonathan Garcia
Hopital Charles-Lemoyne
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Argem Sabuga
McGill University Health Centre
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Maurane Ricard
Hopital Charles-Lemoyne
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France Dion
Hopital Charles-Lemoyne
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Vlad Rosu
McGill University Health Centre
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Marie-Eve Legris
Hopital Charles-Lemoyne
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Amélie Marsot
Université de Montréal
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Van Dong Nguyen
McGill University Health Centre

Corresponding Author:van.dong.nguyen@umontreal.ca

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Abstract

Patients undergoing hemodialysis (HD) are at greater risk of methicillin-resistant Staphylococcus aureus infections requiring intravenous vancomycin. Close vancomycin therapeutic drug monitoring is warranted in HD patients as renal clearance is the primary elimination pathway. Clinically, population pharmacokinetics (popPK) model‐informed dosing is commonly used. This study aimed to perform an external evaluation of published vancomycin popPK models developed for adults undergoing high-flux intermittent HD, and to create a dosing nomogram derived from the best performing model. A literature review was conducted through PubMed and EMBASE to identify relevant popPK models. External dataset was collected retrospectively from patients of two healthcare centers in Quebec, Canada. Selected models were implemented in NONMEM (v7.5; ICON Development Solutions). Predictive performance was assessed through prediction and simulation-based diagnostics. Results analyses and graphical representations were then performed with Microsoft Excel (v16.69.1; Microsoft Office), R (v4.3.1; Posit Software) and R Studio (v1.4; Posit Software). A total of 2386 vancomycin concentrations were collected from 274 patients and 476 antibiotic courses. Four vancomycin popPK models were selected for evaluation. None of the models demonstrated overall satisfactory and clinically acceptable predictive performance. Nonetheless, Bae et al.’s model was the best performing with a MDPE of 16.25% and MDAPE of 34.66%. Different predictive performance was also observed for vancomycin concentrations from samples collected during and between HD sessions. All evaluated models presented poor overall predictive performance. Further studies are required, through existing popPK model parameters re-estimation or new model development, to adequately describe vancomycin pharmacokinetics for our high-flux intermittent HD patients’ cohort.
Submitted to British Journal of Clinical Pharmacology
27 May 2024Review(s) Completed, Editorial Evaluation Pending
12 Jul 2024Editorial Decision: Revise Major
21 Oct 20241st Revision Received
22 Oct 2024Submission Checks Completed
22 Oct 2024Assigned to Editor
22 Oct 2024Review(s) Completed, Editorial Evaluation Pending
28 Oct 2024Editorial Decision: Accept