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Application of physiologically based pharmacokinetics modeling in the research of small-molecule targeted anti-cancer drugs

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Abstract

Introduction

Physiologically based pharmacokinetics (PBPK) models are increasingly used in the drug research and development, especially in anti-cancer drugs. Between 2001 and 2020, a total of 89 small-molecule targeted antitumor drugs were approved in China and the United States, some of which already included PBPK modeling in their application or approval packages. This article intended to review the prevalence and application of PBPK model in these drugs.

Method

Article search was performed in the PubMed to collect English research articles on small-molecule targeted anti-cancer drugs using PBPK modeling. The selected articles were classified into nine categorizes according to the application areas and further analyzed.

Result

From 2001 to 2020, more than 60% of small-molecule targeted anti-cancer drugs (54/89) were studied using PBPK model with a wide range of application. Ninety research articles were included, of which 48 involved enzyme-mediated drug-drug interaction (DDI). Of these retrieved articles, Simcyp, GastroPlus, and PK-Sim were the most widely model building platforms, which account for 63.8%, 15.2%, and 8.6%, respectively.

Conclusion

PBPK modeling is commonly and widely used to research small-molecule targeted anti-cancer drugs.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thanks Qingfeng He, PhD, and **ao Zhu, PhD, for their writing support.

Funding

This project was supported by National Natural Science Foundation of China and National Research Foundation of Korea (No. 82011540409), Minhang District Science and Technology Commission Foundation (No. 2020MHZ035).

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  1. **aowen Wang and Fang Chen contributed equally to this manuscript.

Authors and Affiliations

  1. Department of Pharmacy, Minhang Hospital, Fudan University, 170 **nsong Road, Shanghai, China

    **aowen Wang, Nan Guo & Bing Han

  2. Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, China

    **aowen Wang, **aoqiang **ang & Yufei Shi

  3. Department of Pharmacy, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China

    Fang Chen, Zhichun Gu & Houwen Lin

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  1. **aowen Wang
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XW, FC, ZG, NG, HL, XX, YS, and BH contributed to the data collection and analysis and review; wrote and reviewed the manuscript; and approved the final manuscript for publication.

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Correspondence to Yufei Shi or Bing Han.

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**aowen Wang, Fang Chen, Zhichun Gu, Nan Guo, Houwen Lin, **aoqiang **ang, Yufei Shi, and Bing Han have no conflicts of interest that are directly relevant to the content of this article.

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Wang, X., Chen, F., Guo, N. et al. Application of physiologically based pharmacokinetics modeling in the research of small-molecule targeted anti-cancer drugs. Cancer Chemother Pharmacol 92, 253–270 (2023). https://doi.org/10.1007/s00280-023-04566-z

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