多西他赛用于实体瘤患者的群体药代动力学研究

奚鑫; 董育珠; 赵成龙; 杨佳; 李文军; 杜倩; 刘松青

doi:10.16016/j.2097-0927.202206052

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多西他赛用于实体瘤患者的群体药代动力学研究

药学 | 更新时间：2026-01-09

- 多西他赛用于实体瘤患者的群体药代动力学研究
- Population pharmacokinetics of docetaxel in patients with solid tumors
- 陆军军医大学学报 2022年44卷第22期页码：2330-2339
- 作者机构：
  
  1.401120 重庆, 重庆医科大学附属第三医院药剂科
  2.450000 郑州, 河南省人民医院药学部
- 作者简介：
  
  [杜倩，E-mail: duqian@hospital.cqmu.edu.cn DU Qian, E-mail: duqian@hospital.cqmu.edu.cn
  [刘松青，E-mail: liusongqing@hospital.cqmu.edu.cn LIU Songqing, E-mail: liusongqing@hospital.cqmu.edu.cn
- 基金信息：
  
  重庆市渝中区基础研究与前沿探索项目(20190113)
- DOI：10.16016/j.2097-0927.202206052
  中图分类号： R181.35;R730.53;R979.11
- 收稿：2022-06-09，
  
  修回：2022-08-01，
  
  纸质出版：2022-11-30
- 稿件说明：
移动端阅览
奚鑫, 董育珠, 赵成龙, 等. 多西他赛用于实体瘤患者的群体药代动力学研究[J]. 陆军军医大学学报, 2022,44(22):2330-2339.

Xin XI, Yuzhu DONG, Chenglong ZHAO, et al. Population pharmacokinetics of docetaxel in patients with solid tumors[J]. Journal of Army Medical University, 2022, 44(22): 2330-2339.
奚鑫, 董育珠, 赵成龙, 等. 多西他赛用于实体瘤患者的群体药代动力学研究[J]. 陆军军医大学学报, 2022,44(22):2330-2339. DOI： 10.16016/j.2097-0927.202206052.

Xin XI, Yuzhu DONG, Chenglong ZHAO, et al. Population pharmacokinetics of docetaxel in patients with solid tumors[J]. Journal of Army Medical University, 2022, 44(22): 2330-2339. DOI： 10.16016/j.2097-0927.202206052.

摘要

目的

探讨多西他赛(docetaxel，DTX)在实体肿瘤患者中的药代动力学(pharmacokinetics，PK)特征和变异来源。

方法

收集2018年1月1日至2020年12月31日在重庆医科大学附属第三医院乳甲外科、肿瘤科、胸外科与河南省人民医院乳甲外科、肿瘤科、妇产科两所医院6个科室374名患者的772份DTX血浆样本。采用液相色谱-质谱联用法(LC-MS/MS)测定DTX的血药浓度；应用非线性混合效应模型(nonlinear mixed-effects model

NONMEM)软件进行群体药代动力学(population pharmacokinetics

PPK)数据分析；使用自举法和可视化预测检验(visual predictive check

VPC)进行模型的内部验证。

结果

建立了DTX在实体肿瘤患者群体中一级消除的三房室PPK模型，DTX的血药浓度范围在3.53~2 491 ng/mL，中位数为175.5 ng/mL。白蛋白(albumin

ALB)是显著影响DTX清除率(clearance，

)的协变量，肌酐(creatinine

CREA)是显著影响中央室与周边室2的房室清除率(

)的协变量。模型估算的DTX的

为57.2 L/h，周边室1的分布容积(

)为11.8 L，中央室与周边室1的房室清除率(

)和中央室与周边室2的房室清除率(

)分别为14.1 L/h和8.63 L/h。

结论

在实体肿瘤患者群体中利用多中心数据建立三房室PPK模型，发现ALB是影响

变异的主要因素，内部验证结果表明该模型稳定、可靠。

Abstract

Objective

To explore the characteristics and the cause of variance of pharmacokinetics (PK) of docetaxel (DTX) in patients with solid tumors.

Methods

Between January 1 of 2018 and December 31 of 2020

374 patients at two research centers—oncology

breast and thyroid surgery

thoracic surgery

the Third Affiliated Hospital of Chongqing Medical University

and oncology

breast and thyroid surgery

obstetrics and gynecology

Henan Provincial People's Hospital—provided a total of 772 docetaxel plasma samples. Liquid chromatography-mass spectrometry (LC-MS/MS) was used to determine docetaxel plasma concentrations. Nonlinear mixed-effects model (NONMEM) software was used to establish the population phar macokinetics(PPK) model. Using bootstrap and visual predictive check(VPC) for internal validation of the model.

Results

The current study established a three-compartment PPK model with first-order elimination of docetaxel in patients with solid tumors. DTX blood concentrations ranged from 3.53 ng/mL to 2 491 ng/mL

with a median of 175.5 ng/mL. Albumin (ALB) was identified as a covariate significantly affecting the clearance(

) of docetaxel

and creatinine(CREA) was a covariate significantly affecting

. The model-estimated

and

of docetaxel were 57.2 L/h

11.8 L

14.1 L/h

and 8.63 L/h

respectively.

Conclusion

A three-compartment PPK model with multicenter data is established in patients with solid tumors. ALB is the main factor affecting

variation. The internal validation results show that the model is stable and reliable.

关键词

Keywords

references

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