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Population pharmacokinetics of free and liposome-encapsulated mitoxantrone in patients with relapsed/refractory lymphoma or small cell lung cancer

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Abstract

Objective

This study is aimed at investigating the pharmacokinetic (PK) characteristics of pegylated liposomal mitoxantrone (PLM) in patients with relapsed/refractory lymphoma or small cell lung cancer (SCLC) by constructing population pharmacokinetic (popPK) models for both liposome-encapsulated mitoxantrone and free mitoxantrone.

Methods

A total of 23 patients with relapsed/refractory lymphoma and 42 patients with SCLC were included. A popPK model was simultaneously developed utilizing a non-linear mixed effects model (NONMEM) to explore the PK profiles of liposome-encapsulated mitoxantrone and free mitoxantrone. Clearance (CL) and distribution volume (V) were calculated, and covariate analysis was employed to evaluate the influence of patient disease type, demographic information, and biochemical indicators of liver and kidney function on PK parameters.

Results

The concentration-time profiles for both liposome-encapsulated mitoxantrone and free mitoxantrone were described by a one-compartment model. The release (Rel) of liposome-encapsulated mitoxantrone to free mitoxantrone was determined to be 0.0191 L/h, and the V of liposome-encapsulated mitoxantrone was 2.32 L. The apparent CL of free mitoxantrone was estimated at 1.66 L/h. The apparent V of free mitoxantrone was 35.8 L in patients with relapsed/refractory lymphoma and 22.2 L for patients with SCLC. In patients with relapsed/refractory lymphoma, lower maximum concentration (Cmax) and higher apparent V of free mitoxantrone were observed compared with patients with SCLC.

Conclusion

The popPK characteristics of both liposome-encapsulated and free mitoxantrone in patients with relapsed/refractory lymphoma or SCLC were effectively described by a one-compartment model.

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Data availability

No datasets were generated or analysed during the current study.

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Author information

Author notes

  1. Gaoqi Xu and Dihong Yang contributed equally to this study.

Authors and Affiliations

  1. Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China

    Gaoqi Xu, Dihong Yang, Haiying Ding, Like Zhong, Junfeng Zhu, **ufang Mi, Wenxiu **n, Jiaqi Wang & Luo Fang

  2. CSPC Zhongqi Pharmaceutical Technology (SJZ) Co., Ltd., Shijiazhuang, Hebei, 050035, China

    Xueyuan Zhang, Zhufeng Wu & Chunlei Li

Authors
  1. Gaoqi Xu
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Contributions

CL, JW, and LF contributed to the study concept and design. XZ, CL, and LF contributed to data collection. XM and WX checked the integrity of the data and the accuracy of the data analysis. GX and DY analyzed the data. GX, HD, and LZ drafted the manuscript. All authors commented on drafts of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Chunlei Li, Jiaqi Wang or Luo Fang.

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Ethical approval

The studies involving human participants were reviewed and approved by the Ethics Committee of the Guizhou Medical University and West China Hospital of Sichuan University. The patients provided their written informed consent to participate in both studies.

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All authors read and approved the final manuscript for publication.

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The authors declare no competing interests.

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Xu, G., Yang, D., Ding, H. et al. Population pharmacokinetics of free and liposome-encapsulated mitoxantrone in patients with relapsed/refractory lymphoma or small cell lung cancer. Eur J Clin Pharmacol (2024). https://doi.org/10.1007/s00228-024-03711-8

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