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External evaluation of population pharmacokinetic models for continuous administration of meropenem in critically ill adult patients

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Beta-lactams (BL), the most commonly prescribed class of antibiotics, are recommended as the first-line therapy for multiple indications in infectious disease guidelines. Meropenem (MERO) is frequently used in intensive care units (ICU) to treat bacterial infections with or without sepsis. The pharmacokinetics of MERO display a large variability in patients admitted to ICUs due to altered pathophysiology. The aim of this study was to perform an external evaluation of published population pharmacokinetic models of MERO in order to test their predictive performance in a cohort of ICU adult patients.

Methods

A literature search in PubMed/Medline database was made following the PRISMA statement. External evaluation was performed using NONMEM software, and the bias and inaccuracy values were calculated.

Results

An external validation dataset from the Timone Hospital in Marseille, France, included 84 concentration samples from 27 patients. Four models of MERO were identified according to the inclusion criteria of the study. None of the models presented acceptable values of bias and inaccuracy.

Conclusion

While performing external evaluations on some populations may confirm a model’s suitability to diverse groups of patients, there is still some variability that cannot be explained nor solved by the procedure. This brings to light the difficulty to develop only one model for ICU patients and the need to develop one specific model to each population of critically ill patients.

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Funding

Internal funding supported this study.

Author information

Authors and Affiliations

  1. Laboratoire de Suivi Thérapeutique Pharmacologique et Pharmacocinétique, Faculté de Pharmacie, Université de Montréal, Pavillon Jean-Coutu, 2940 chemin de Polytechnique, Montréal, QC, H3T 1J4, Canada

    YL. Wang & Amélie Marsot

  2. Faculté de Pharmacie, Université de Montréal, Montréal, QC, Canada

    YL. Wang & Amélie Marsot

  3. Service de Pharmacologie Clinique et Pharmacovigilance, Hôpital de la Timone, Assistance Publique des Hôpitaux de Marseille, Marseille, France

    R. Guilhaumou & O. Blin

  4. Pharmacologie intégrée et interface clinique et industrielle, Institut de Neuroscience des systèmes, CNRS 7289, Aix Marseille Université, 13385, Marseille, France

    R. Guilhaumou & O. Blin

  5. Service d’Anesthésie-Réanimation, Hôpital de la Timone, Assistance Publique des Hôpitaux de Marseille, Marseille, France

    L. Velly

  6. Centre de Recherche, CHU Sainte Justine, Montréal, QC, Canada

    Amélie Marsot

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  1. YL. Wang
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Contributions

YW and AM analyzed the data. AM performed population pharmacokinetic analysis. LV included patient. YW and AM wrote the manuscript. OB validated the manuscript. AM and RG conceived and designed the study. AM supervised the work. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Amélie Marsot.

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Wang, Y., Guilhaumou, R., Blin, O. et al. External evaluation of population pharmacokinetic models for continuous administration of meropenem in critically ill adult patients. Eur J Clin Pharmacol 76, 1281–1289 (2020). https://doi.org/10.1007/s00228-020-02922-z

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  • DOI: https://doi.org/10.1007/s00228-020-02922-z

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