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Micafungin Population PK Analysis in Healthy and Septic Pigs: Can the Septic Porcine Model Predict the Micafungin PK in Septic Patients?

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Abstract

Objectives

To describe micafungin pharmacokinetic (PK) alterations of sepsis induced in piglets and to determine whether the porcine septic model is able to predict the PK of micafungin in septic patients at the plasma and peritoneal sites.

Methods

From healthy (n = 8) and septic piglet group (n = 16), total micafungin concentrations were subject to a population PK analysis using Monolix®. Data from 16 septic humans patients from others studies was used to compare micafungin PK between septic piglets and septic patients.

Results

Sepsis induced in piglets slightly alters the total clearance and the volume of distribution, while inter-compartment clearance is increased (from 3.88 to 5.74 L/h) as well as the penetration into peritoneal cavity (from 61 to 90%). In septic human patients, PK parameters are similar except for the Vd, which is corrected by an allometric factor based on the body weight of each species. Micafungin penetration into peritoneal cavity of humans is lower than in septic piglets (40 versus 90%).

Conclusions

The sepsis induced in the porcine model alters the PK of micafungin comparable to that in humans. In addition, micafungin PK is similar between these two species at the plasma level taking into account the allometric relationship of the body weight of these species on the central volume of distribution. The porcine septic plasma model would be able to predict the micafungin PK in the septic patients. However, further studies on peritoneal penetration are necessary to characterize this inter-species difference.

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Funding

This study was supported by an academic funding from the Nimes University Hospital to conduct this work.

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Authors and Affiliations

  1. Service Des Réanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Nîmes, France

    Nicolas Garbez, Guillaume Louart, Laurent Muller, Jean-Yves Lefrant & Claire Roger

  2. Laboratoire de Pharmacocinétique, Faculté de Pharmacie, Université de Montpellier, Montpellier, France

    Nicolas Garbez & Litaty C. Mbatchi

  3. UR-UM 103: IMAGINE (Initial Management And Prévention of orGan Failures IN Critically Ill patiEnts), Faculté de Médecine, Université de Montpellier, Montpellier, France

    Nicolas Garbez, Guillaume Louart, Laurent Muller, Jeffrey Lipman, Jason A. Roberts, Jean-Yves Lefrant & Claire Roger

  4. Laboratoire de Biochimie, Centre Hospitalier Universitaire (CHU) of Nîmes, Hôpital Carémeau, Nîmes, France

    Litaty C. Mbatchi

  5. UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia

    Steven C. Wallis, Jeffrey Lipman & Jason A. Roberts

  6. Jamieson Trauma Institute and Intensive Care Services, Royal Brisbane and Womens’ Hospital, Brisbane, QLD, Australia

    Jeffrey Lipman & Jason A. Roberts

  7. Centre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia

    Jason A. Roberts

  8. Pharmacy Department, Royal Brisbane and Womens’ Hospital, Brisbane, QLD, Australia

    Jason A. Roberts

Authors
  1. Nicolas Garbez
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  2. Litaty C. Mbatchi
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  3. Guillaume Louart
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  4. Steven C. Wallis
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  5. Laurent Muller
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  6. Jeffrey Lipman
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  7. Jason A. Roberts
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  8. Jean-Yves Lefrant
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  9. Claire Roger
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Corresponding author

Correspondence to Nicolas Garbez.

Ethics declarations

Jeffrey Lipman received honoraria from MSD and Pfizer and received Institution support from MSD. Claire Roger received consultancy fees from MSD, Pfizer, and Fresenius Medical Care.

Nicolas Garbez, Litaty Mbatchi, Guillaume Louart, Steven C. Wallis, Laurent Muller, Jason A. Roberts, Jean-Yves Lefrant have no conflict of interest to declare.

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Garbez, N., Mbatchi, L.C., Louart, G. et al. Micafungin Population PK Analysis in Healthy and Septic Pigs: Can the Septic Porcine Model Predict the Micafungin PK in Septic Patients?. Pharm Res 38, 1863–1871 (2021). https://doi.org/10.1007/s11095-021-03137-2

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  • DOI: https://doi.org/10.1007/s11095-021-03137-2

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