阿米卡星在老年肾功能不全患者中生理药动学模型的建立与应用

李乔希; 管宴萍; 夏晨; 吴莉莉; 王妍

doi:10.6039/j.issn.1001-0408.2023.18.14

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阿米卡星在老年肾功能不全患者中生理药动学模型的建立与应用

药物与临床 | 更新时间：2023-09-22

- 阿米卡星在老年肾功能不全患者中生理药动学模型的建立与应用
- Establishment and application of the physiologically-based pharmacokinetic model of amikacin in elderly patients with renal insufficiency
- 中国药房 2023年34卷第18期页码：2250-2255
- 作者机构：
  
  1.佛山市第一人民医院药学部，广东佛山　528000
  2.中山大学药学院临床药理研究所，广州　510030
- 作者简介：
  
  药师，硕士。研究方向：药动学、定量药理。E-mail：liqiaoxi4321@foxmail.com
  副主任药师，博士。研究方向：临床药学、医院药事管理。E-mail：wangyantj2008@aliyun.com
- 基金信息：
  
  广东省医院药学研究基金（澳美基金）(2021A42)
- DOI：10.6039/j.issn.1001-0408.2023.18.14
  中图分类号： R969.1
- 纸质出版日期：2023-09-30，
  
  收稿日期：2023-03-19，
  
  修回日期：2023-08-26，
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李乔希,管宴萍,夏晨等.阿米卡星在老年肾功能不全患者中生理药动学模型的建立与应用 ^Δ[J].中国药房,2023,34(18):2250-2255.

LI Qiaoxi,GUAN Yanping,XIA Chen,et al.Establishment and application of the physiologically-based pharmacokinetic model of amikacin in elderly patients with renal insufficiency[J].ZHONGGUO YAOFANG,2023,34(18):2250-2255.
李乔希,管宴萍,夏晨等.阿米卡星在老年肾功能不全患者中生理药动学模型的建立与应用 ^Δ[J].中国药房,2023,34(18):2250-2255. DOI： 10.6039/j.issn.1001-0408.2023.18.14.

LI Qiaoxi,GUAN Yanping,XIA Chen,et al.Establishment and application of the physiologically-based pharmacokinetic model of amikacin in elderly patients with renal insufficiency[J].ZHONGGUO YAOFANG,2023,34(18):2250-2255. DOI： 10.6039/j.issn.1001-0408.2023.18.14.

摘要

目的

建立阿米卡星在老年肾功能不全患者中的生理药动学（PBPK）模型。

方法

使用PK-SIM

软件进行模型的构建、拟合和模拟。通过查询文献资料，收集阿米卡星的理化性质和体内药动学特性参数，结合软件内置人体模型建立成人PBPK模型并外推至老年PBPK模型。使用临床药动学研究数据对模型进行拟合优化和验证，以拟合优度、相对残差和平均折叠误差为指标评价模型预测性能。使用最终模型模拟老年肾功能不全患者给药后的体内暴露情况，对临床常用给药方案的有效性和安全性进行评估，并给出推荐的给药方案。

结果

建立的阿米卡星PBPK模型在成人和老年患者中均有较好的预测性能，相对残差绝对值均数为25%；各模拟场合下，峰浓度（

max

）和药时曲线下面积（AUC

0－∞

）的平均折叠误差均在＞0.5～＜2范围内。模拟结果显示，与健康成人相比，相同给药方案下老年肾功能不全患者的

max

差异较小，因蓄积引起的谷浓度显著升高。与减少剂量相比，延长阿米卡星给药间隔更有助于保证疗效，减少肾毒性的发生。

结论

成功建立了阿米卡星在老年肾功能不全患者中的PBPK模型，且模型具有良好的预测性能。

Abstract

OBJECTIVE

To establish a physiologically-based pharmacokinetic （PBPK） model of amikacin in elderly patients with renal insufficiency.

METHODS

PK-SIM

software was adopted for model building， optimization and simulation. The physical and chemical properties and pharmacokinetic parameters related to amikacin were collected by literature review. The PBPK model on adults was established and extrapolated to the elderly population based on the built-in human model. Data from clinical PK studies were used to optimize and validate the model. The goodness of fit， relative residual， and mean folding error （MFE） were used to evaluate the performance of forecasting. The final model was employed to simulate the exposure of amikacin in the elderly population with renal insufficiency， and the efficacy and safety of commonly used clinical dosing regimens were evaluated， and the recommended regimens were proposed.

RESULTS

The established PBPK model of amikacin had good prediction performance in both adult and elderly populations， with the absolute mean of relative residual value of 25%； the MFE of peak concentration （

max

） and area under the plasma concentration curve （AUC

0－∞

） in all simulation occasions ranged ＞0.5-＜2. The simulation results showed that， compared with healthy adults， no significant clinical difference in

max

was observed in the elderly with renal insufficiency at the same dosing regimen， but the trough concentration increased significantly due to accumulation. Prolonging the administration interval of amikacin rather than reducing the dosage was more helpful to ensure the efficacy and to reduce the occurrence of nephrotoxicity.

CONCLUSIONS

The PBPK model for amikacin is successfully established in the elderly patient with renal insufficiency， and shows good predictive performance.

关键词

阿米卡星药动学生理药动学模型老年人肾功能不全

Keywords

pharmacokineticsphysiologically-based pharmacokinetic modelthe elderlyrenal insufficiency

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