Population pharmacokinetic model library for isavuconazole: development and quality control
4 affiliations
- 1Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
- 2Research Center for Clinical Pharmacy, College of Pharmaceutical Science, Zhejiang University
- 3Department of Pharmacy, Affiliated Xiaoshan Hospital, Hangzhou Normal University
- 4Department of Pharmacy, First Affiliated Hospital of Wenzhou Medical University
Abstract
Background and objective: Isavuconazole is the first-line option for the treatment of invasive aspergillosis and mucormycosis. However, it has large pharmacokinetic (PK) variabilities, and suboptimal exposure is concerned. This study aimed to develop an isavuconazole population pharmacokinetic (PPK) library that contributes to model-informed precision dosing (MIPD) and dose optimization.
Methods: Following a systematic literature search and study inclusion, a library of isavuconazole PPK models was developed. The model characteristics and parameters estimated were extracted and compared. The AUC distributions at steady status across different models were compared, and the effects of covariates on PK parameters were analyzed. The model library was used to estimate target achievement with the PK/PD target of AUC/MIC 33 for Aspergillus through Monte Carlo simulations.
Results: A total of 955 unduplicated records were initially identified from PubMed, Web of Science, and Embase. After screening and eligibility assessment, 14 studies were ultimately included in the model library. The quality scores of the included studies ranged from 35 to 45. The included PPK models had high reporting quality and covered a diversity of patients, with the two-compartment model being the most common. The total clearance of isavuconazole ranged from 1.33–5.34 L/h. Body weight, body surface area (BSA), body mass index (BMI), albumin levels, and liver function markers were the most common significant covariates, and their overall impact met the clinically significant criteria. The simulation results indicate that for a susceptive threshold of MIC 1 mg/L, most models (11/14) achieved PTA over 90%, while dose optimization may be required for critically ill patients, hematological patients and patients with abnormal covariates.
Conclusion: This study successfully developed a PPK library for isavuconazole, which would support the precision dosing of isavuconazole.
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BibTeX
@article{tang2026population,
title = {{Population pharmacokinetic model library for isavuconazole: development and quality control}},
author = {Qing Tang and Yuhua Zhao and Jianping Zhu and Jieqiong Liu and Gang Liang and Yi Yang and Renai Xu and Zhenwei Yu},
journal = {Frontiers in Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1930025},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1930025/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Population pharmacokinetic model library for isavuconazole: development and quality control
AU - Qing Tang
AU - Yuhua Zhao
AU - Jianping Zhu
AU - Jieqiong Liu
AU - Gang Liang
AU - Yi Yang
AU - Renai Xu
AU - Zhenwei Yu
PY - 2026
DA - 2026/10/06
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1930025
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1930025/full
AB - Background and objective: Isavuconazole is the first-line option for the treatment of invasive aspergillosis and mucormycosis. However, it has large pharmacokinetic (PK) variabilities, and suboptimal exposure is concerned. This study aimed to develop an isavuconazole population pharmacokinetic (PPK) library that contributes to model-informed precision dosing (MIPD) and dose optimization. Methods: Following a systematic literature search and study inclusion, a library of isavuconazole PPK models was developed. The model characteristics and parameters estimated were extracted and compared. The AUC distributions at steady status across different models were compared, and the effects of covariates on PK parameters were analyzed. The model library was used to estimate target achievement with the PK/PD target of AUC/MIC 33 for Aspergillus through Monte Carlo simulations. Results: A total of 955 unduplicated records were initially identified from PubMed, Web of Science, and Embase. After screening and eligibility assessment, 14 studies were ultimately included in the model library. The quality scores of the included studies ranged from 35 to 45. The included PPK models had high reporting quality and covered a diversity of patients, with the two-compartment model being the most common. The total clearance of isavuconazole ranged from 1.33–5.34 L/h. Body weight, body surface area (BSA), body mass index (BMI), albumin levels, and liver function markers were the most common significant covariates, and their overall impact met the clinically significant criteria. The simulation results indicate that for a susceptive threshold of MIC 1 mg/L, most models (11/14) achieved PTA over 90%, while dose optimization may be required for critically ill patients, hematological patients and patients with abnormal covariates. Conclusion: This study successfully developed a PPK library for isavuconazole, which would support the precision dosing of isavuconazole.
SN - 1664-302X
ER -