Development of a physiologically based pharmacokinetic model for vancomycin in hemodialysis patients

ZHOU Chuyi; LIU Ganghui; CAI Junlong; SHEN Yiwei; WU Jianyuan

doi:10.14188/j.1671-8852.2026.1145

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Development of a physiologically based pharmacokinetic model for vancomycin in hemodialysis patients

更新时间：2026-11-05

- Development of a physiologically based pharmacokinetic model for vancomycin in hemodialysis patients
- Medical Journal of Wuhan University Vol. 47, Issue 10, Pages: 1352-1358(2026)
- 作者机构：
  
  1.武汉大学中南医院临床试验中心湖北武汉 430071
  2.武汉大学药学院湖北武汉 430071
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2026.1145
  CLC： R969
- Received：09 July 2026，
  
  Published：25 October 2026
- 稿件说明：
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周楚宜,刘港辉,蔡君龙等.血液透析患者万古霉素生理药代动力学模型的建立[J].武汉大学学报（医学版）,2026,47(10):1352-1358.

ZHOU Chuyi,LIU Ganghui,CAI Junlong,et al.Development of a physiologically based pharmacokinetic model for vancomycin in hemodialysis patients[J].Medical Journal of Wuhan University,2026,47(10):1352-1358.
周楚宜,刘港辉,蔡君龙等.血液透析患者万古霉素生理药代动力学模型的建立[J].武汉大学学报（医学版）,2026,47(10):1352-1358. DOI： 10.14188/j.1671-8852.2026.1145.

ZHOU Chuyi,LIU Ganghui,CAI Junlong,et al.Development of a physiologically based pharmacokinetic model for vancomycin in hemodialysis patients[J].Medical Journal of Wuhan University,2026,47(10):1352-1358. DOI： 10.14188/j.1671-8852.2026.1145.

摘要

目的

构建万古霉素在血液透析患者中的生理药代动力学(PBPK)模型，并进行药代动力学（PK）行为预测。

方法

结合万古霉素的理化参数、药代动力学参数及已发表临床数据，使用Phoenix WinNonlin软件建立健康成人PBPK模型，并将其外推至血液透析治疗患者，通过参数优化预测万古霉素在透析患者中个体的PK代谢特征，采用文献已报道的万古霉素临床数据进行模型验证，当折叠误差即预测值与实测值比值在0.5~2之间认为模型预测效果较为理想。

结果

参考文

献报道的55例健康成人单次给药、38例健康成人多次给药数据以及9例血液透析患者给药数据，验证建立的健康人和血液透析患者PBPK模型具有较为理想的准确性和适用性，观测值与预测值曲线的重合度良好，误差较小，PBPK核心参数

max

、

AUC

0⁃t

的折叠误差值均在0.5~2范围内。本研究构建的PBPK模型通过参数选择、结合对该药分布和清除方式的假设及考虑，能够比较准确地反映出万古霉素在血液透析患者个体内吸收和处置过程，具有较好的准确性及适用性。

结论

所建立的PBPK模型可较准确地预测万古霉素在血液透析治疗患者体内的PK特征，可进一步用于优化给药方案，为临床个体化用药提供参考。

Abstract

Objective

To develop a physiologically based pharmacokinetic (PBPK) model of vancomycin in patients receiving hemodialysis therapy and to predict its pharmacokinetic (PK) behavior.

Methods

By integrating the physicochemical properties

pharmacokinetic parameters

and published clinical data of vancomycin

a PBPK model was established in healthy adults by using Phoenix WinNonlin software and subsequently extrapolated to patients undergoing hemodialysis. Parameter optimization was performed to predict the individual pharmacokinetic profiles of vancomycin in dialysis patients. The model was validated using published clinical data of vancomycin

and predictive performance was assessed by fold error (FE)

defined as the ratio of predicted to observed values

with a value between 0.5 and 2 considered indicative of satisfactory predictive performance.

Results

The established PBPK models for healthy adults and hemodialysis patients were validated using data from 55 healthy adults receiving single⁃dose administration

38 healthy adults receiving multiple⁃dose administration

and 9 hemodialysis patients

as reported in the literature. The validation demonstrated good accuracy and applicability of the models

as evidenced by close agreement between observed and predicted concentration⁃time curves with minimal prediction errors. The fold error values for key PBPK indices C

max

and

AUC

0⁃t

fell within the acceptable range of 0.5–2.

Conclusion

The established PBPK model can successfully predict the pharmacokinetic characteristics of vancomycin in patients receiving hemodialysis therapy and may be further applied to optimize dosing regimens

thereby providing a reference for individualized drug therapy in clinical practice.

关键词

Keywords

references

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