Prediction of the drug-drug interaction between sodium tanshinone Ⅱ<sub>A</sub> sulfonate and clopidogrel based on the PBPK model

ZHANG Die; ZHANG Lichao; SUN Mengru; QIAN Fengdan

doi:10.6039/j.issn.1001-0408.2026.13.15

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Prediction of the drug-drug interaction between sodium tanshinone Ⅱ_A sulfonate and clopidogrel based on the PBPK model

更新时间：2026-07-10

- Prediction of the drug-drug interaction between sodium tanshinone Ⅱ_A sulfonate and clopidogrel based on the PBPK model
- ZHONGGUO YAOFANG Vol. 37, Issue 13, Pages: 1746-1750(2026)
- 作者机构：
  
  上海中医药大学附属市中医医院药学部，上海　201800
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2026.13.15
  CLC： R969.2
- Received：13 January 2026，
  
  Revised：2026-06-11，
  
  Accepted：15 June 2026，
  
  Published：15 July 2026
- 稿件说明：
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张蝶,张立超,孙梦茹,等.基于PBPK模型预测丹参酮Ⅱ_A磺酸钠与氯吡格雷联用的药物相互作用[J].中国药房,2026,37(13):1746-1750. DOI: 10.6039/j.issn.1001-0408.2026.13.15.

ZHANG Die,ZHANG Lichao,SUN Mengru,et al.Prediction of the drug-drug interaction between sodium tanshinone Ⅱ_A sulfonate and clopidogrel based on the PBPK model[J].ZHONGGUO YAOFANG,2026,37(13):1746-1750. DOI: 10.6039/j.issn.1001-0408.2026.13.15.
张蝶,张立超,孙梦茹,等.基于PBPK模型预测丹参酮Ⅱ_A磺酸钠与氯吡格雷联用的药物相互作用[J].中国药房,2026,37(13):1746-1750. DOI: 10.6039/j.issn.1001-0408.2026.13.15. DOI：

ZHANG Die,ZHANG Lichao,SUN Mengru,et al.Prediction of the drug-drug interaction between sodium tanshinone Ⅱ_A sulfonate and clopidogrel based on the PBPK model[J].ZHONGGUO YAOFANG,2026,37(13):1746-1750. DOI: 10.6039/j.issn.1001-0408.2026.13.15. DOI：

摘要

目的

构建丹参酮Ⅱ

磺酸钠（STS）与氯吡格雷（Clo）及其代谢产物的生理学药代动力学（PBPK）模型，预测二者联用时的药物相互作用（DDI），并分析影响DDI的关键因素，为临床合理用药提供参考。

方法

检索PubMed、DrugBank、SwissADME，收集Clo及其代谢产物与STS的理化特征参数，构建两药及其代谢产物的PBPK模型。以Clo硫醇代谢产物（Clo-AM）的稳态血浆浓度-时间曲线下面积（AUC）和最大血浆浓度（

max

）为指标，评估STS与Clo联用时的DDI；采用单因素敏感性分析筛选影响STS与Clo联用时DDI的关键因素。

结果

与单用Clo相比，Clo联用STS 40 mg 7 d后，Clo-AM的AUC比值和

max

比值分别为0.75和0.63；当STS剂量增加至80 mg时，Clo-AM的AUC比值和

max

比值进一步下降至0.62和0.56。敏感性分析结果表明，Clo-AM的脂溶性、STS-CYP2C19抑制常数、STS-CYP3A4抑制常数、Clo-AM的肝清除率的归一化敏感性系数的绝对值分别为15.19、11.34、10.98、3.08，为STS与Clo联用时DDI的高敏感参数。

结论

所建PBPK模型可用于预测STS与Clo联用时的DDI；STS与Clo联用可能导致Clo-AM暴露水平下降；Clo-AM的脂溶性参数以及CYP3A4、CYP2C19的抑制参数是影响Clo-AM暴露的关键因素，其中STS对CYP3A4和CYP2C19的抑制作用可能是介导其与Clo发生DDI的重要机制。

Abstract

OBJECTIVE

To develop physiologically based pharmacokinetic （PBPK） model for sodium tanshinone Ⅱ

sulfonate （STS）， clopidogrel （Clo）， and its metabolites， to predict the potential drug-drug interaction （DDI） between STS and Clo during co-administration， and to identify the key factors influencing the predicte

d DDI， and provide evidence for rational clinical medication.

METHODS

Physicochemical and pharmacokinetic parameters of Clo， its metabolites， and STS were retrieved from PubMed， DrugBank， and SwissADME for PBPK model development. The steady-state area under the plasma concentration-time curve （AUC） and maximum concentration （

max

） of clopidogrel thiol H4 （Clo-AM） were used as indicators to evaluate the DDI between STS and Clo. Single-factor sensitivity analysis was performed to identify key parameters influencing DDI between STS and Clo during co-administration.

RESULTS

Compared with Clo alone， after 7 days of Clo combined with STS 40 mg， the AUC ratio and

max

ratio of Clo-AM were 0.75 and 0.63， respectively. When the dose of STS was increased to 80 mg， the AUC ratio and

max

ratio of Clo-AM were 0.62 and 0.56， respectively. Sensitivity analysis indicated that the absolute values of normalized sensitivity coefficients for the lipophilicity of Clo-AM， the inhibition constants of STS for CYP2C19 and CYP3A4， and the hepatic clearance of Clo-AM were 15.19， 11.34， 10.98， 3.08， respectively. These parameters were the highly sensitive parameters in the DDI between STS and Clo during co-administration.

CONCLUSIONS

The established PBPK model can be used to predict the DDI between STS and Clo during co-administration. Co-administration of STS and Clo may lead to decreased exposure of Clo-AM. The lipophilicity-related parameters of Clo-AM and the inhibition parameters related to CYP3A4 and CYP2C19 are key parameters influencing the prediction of Clo-AM exposure， among which the inhibitory effects of STS on CYP3A4 and CYP2C19 may be an important mechanism mediating the DDI between STS and Clo.

关键词

Keywords

references

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Prediction of the drug-drug interaction between sodium tanshinone ⅡA sulfonate and clopidogrel based on the PBPK model

DOI：10.6039/j.issn.1001-0408.2026.13.15

摘要

Abstract

关键词

Keywords

references

Prediction of the drug-drug interaction between sodium tanshinone Ⅱ_A sulfonate and clopidogrel based on the PBPK model