Study on population pharmacokinetics of dabigatran in elderly patients with non-valvular atrial fibrillation

ZHAO Qinhong; QU Yuchen; YANG Yezhou; SHEN Zhu; TAO Hong; ZHU Zhu

doi:10.6039/j.issn.1001-0408.2023.14.14

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Study on population pharmacokinetics of dabigatran in elderly patients with non-valvular atrial fibrillation

更新时间：2023-07-24

- Study on population pharmacokinetics of dabigatran in elderly patients with non-valvular atrial fibrillation
- ZHONGGUO YAOFANG Vol. 34, Issue 14, Pages: 1734-1738(2023)
- 作者机构：
  
  苏州大学附属第二医院药学部，江苏苏州　215004
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.14.14
  CLC： R972;R969.1
- Published：30 July 2023，
  
  Received：01 November 2022，
  
  Revised：26 June 2023，
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赵琴虹,屈昱晨,杨叶舟等.非瓣膜性房颤老年患者达比加群的群体药动学研究 ^Δ[J].中国药房,2023,34(14):1734-1738.

ZHAO Qinhong,QU Yuchen,YANG Yezhou,et al.Study on population pharmacokinetics of dabigatran in elderly patients with non-valvular atrial fibrillation[J].ZHONGGUO YAOFANG,2023,34(14):1734-1738.
赵琴虹,屈昱晨,杨叶舟等.非瓣膜性房颤老年患者达比加群的群体药动学研究 ^Δ[J].中国药房,2023,34(14):1734-1738. DOI： 10.6039/j.issn.1001-0408.2023.14.14.

ZHAO Qinhong,QU Yuchen,YANG Yezhou,et al.Study on population pharmacokinetics of dabigatran in elderly patients with non-valvular atrial fibrillation[J].ZHONGGUO YAOFANG,2023,34(14):1734-1738. DOI： 10.6039/j.issn.1001-0408.2023.14.14.

摘要

目的

分析影响非瓣膜性房颤老年患者达比加群暴露的因素。

方法

收集2019年1月－2020年6月于我院就诊并确诊为非瓣膜性房颤的75例患者资料，每位患者采集1～2个稳态血药浓度样本。采用NONMEM 7.2.0软件建立患者的达比加群群体药动学模型，考察不同协变量对达比加群表观清除率的影响，并通过拟合优度及Bootstrap法对最终模型进行验证；采用NONMEM 7.2.0软件分析不同疾病状态下普通老年患者及高龄老年患者服用达比加群酯后的药物暴露。

结果

共采集到122个达比加群的血药浓度样本。高龄、肌酐清除率及慢性心力衰竭史是影响老年患者达比加群清除率的显著协变量。高龄老年患者暴露相比于普通老年患者增加约50%，合并慢性心力衰竭患者相比于未合并慢性心力衰竭患者暴露增加近30%，中、重度肾功能损伤患者相比于轻度肾功能损伤患者暴露分别增加约30%、80%。

结论

高龄、肾功能损伤、慢性心力衰竭史是引起达比加群体内暴露增加的影响因素。

Abstract

OBJECTIVE

To analyze influential factors for dabigatran exposure in elderly patients with non-valvular atrial fibrillation.

METHODS

The clinical information of 75 elderly patients diagnosed with non-valvular atrial fibrillation was collected from our hospital in Jan. 2019-Jun. 2020. One or two steady-state blood drug concentration samples were collected from each patient. NONMEM 7.2.0 software was used to establish a population pharmacokinetics model of dabigatran； the effects of different covariates on the apparent clearance of dabigatran were investigated， and the final model was verified by goodness of fit and Bootstrap method； NONMEM 7.2.0 software was used to analyze the drug exposure of ordinary elderly patients and elderly patients after taking dabigatran ester in different disease states.

RESULTS

Totally 122 blood concentration samples of dabigatran were collected. Advanced age， creatinine clearance and history of chronic heart failure were screened out as three significant covariates that influenced the clearance of dabigatran in elderly patients. The exposure of population with advanced age increased by about 50% compared with the general elderly， the exposure of population with history of chronic heart failure increased by nearly 30% compared with population without， and the exposure of population with moderate and severe renal injury increased by about 30% and 80% compared with mild.

CONCLUSIONS

Advanced age， renal injury and history of chronic heart failure are influential factors for elevated systemic exposure of dabigatran.

关键词

达比加群非瓣膜性房颤群体药动学老年患者

Keywords

non-valvular atrial fibrillationpopulation pharmacokineticselderly patient

references

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