Comparison of the predictive accuracy of the physiologically based pharmacokinetic (PBPK) model and population pharmacokinetic (PPK) model of vancomycin in Japanese patients with MRSA infection

Takumi Maruyama; Toshimi Kimura; Fumiya Ebihara; Hidefumi Kasai; Nobuaki Matsunaga; Yukihiro Hamada

doi:10.1016/j.jiac.2023.08.017

Comparison of the predictive accuracy of the physiologically based pharmacokinetic (PBPK) model and population pharmacokinetic (PPK) model of vancomycin in Japanese patients with MRSA infection

J Infect Chemother. 2023 Dec;29(12):1152-1159. doi: 10.1016/j.jiac.2023.08.017. Epub 2023 Sep 4.

Authors

Takumi Maruyama¹, Toshimi Kimura², Fumiya Ebihara¹, Hidefumi Kasai³, Nobuaki Matsunaga⁴, Yukihiro Hamada⁵

Affiliations

¹ Department of Pharmacy, Tokyo Women's Medical University Hospital, 8-1, Kawadacho, Shinjuku-ku, Tokyo, 162-8666, Japan.
² Department of Pharmacy, Juntendo University Hospital, 3-1-3 Hongo, Bunkyo-ku, Tokyo, 113-8431, Japan.
³ Laboratory of Pharmacometrics and Systems Pharmacology Keio Frontier Research and Education Collaboration Square (K-FRECS) at Tonomachi, Keio University Kawasaki, Kanagawa, 210-0821, Japan.
⁴ AMR Clinical Reference Center, National Center for Global Health and Medicine Hospital, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
⁵ Department of Pharmacy, Tokyo Women's Medical University Hospital, 8-1, Kawadacho, Shinjuku-ku, Tokyo, 162-8666, Japan. Electronic address: hamada.yukihiro@twmu.ac.jp.

PMID: 37673298
DOI: 10.1016/j.jiac.2023.08.017

Abstract

Introduction: The latest therapeutic drug monitoring guidelines for vancomycin (VCM) recommend that area under the concentration-time curve is estimated based on model-informed precision dosing and used to evaluate efficacy and safety. Therefore, we predicted VCM concentrations in individual methicillin-resistant Staphylococcus aureus-infected patients using existing a physiologically based pharmacokinetic (PBPK) model and 1- and 2-compartment population pharmacokinetic (PPK) models and confirmed and verified the accuracy of the PBPK model in estimating VCM concentrations with the PPK model.

Methods: The subjects of the study are 20 patients, and the predicted concentrations were evaluated by comparing the observed and predicted trough and peak values of VCM concentrations for individual patients.

Results: The results showed good correlation between the observed and predicted trough and peak concentrations of VCM was observed generally in the PBPK model, R² values of 0.72, 0.62, and 0.40 with trough values of 0.49, 0.40, and 0.34 with peak values for PBPK model, 1-compartment, and 2-compartment model, respectively.

Conclusions: Although the performance of the PBPK model is not as predictive as the PPK model, generally similar predictive trends were obtained, suggesting that it may be a valuable tool for rapid and accurate prediction of AUC for VCM.

Keywords: Model-informed precision dosing; Physiologically based pharmacokinetic model; Population pharmacokinetic model; Therapeutic drug monitoring; Vancomycin.

Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.