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中国临床药理学与治疗学 ›› 2024, Vol. 29 ›› Issue (11): 1288-1294.doi: 10.12092/j.issn.1009-2501.2024.11.011

• 临床药理学 • 上一篇    下一篇

基于生理药代动力学模型预测肝损伤患者伏立康唑药代动力学

朱丽娜,董吉,郑利   

  1. 苏州大学附属第一医院药学部,苏州  215000,江苏
  • 收稿日期:2023-11-29 修回日期:2024-03-20 出版日期:2024-11-26 发布日期:2024-10-24
  • 通讯作者: 郑利,男,主要从事临床药学研究。 E-mail: 278880835@qq.com
  • 作者简介:朱丽娜,女,主管药师,研究方向:个体化用药。 E-mail: 33260820@qq.com
  • 基金资助:
    苏州市科技发展计划(SKJYD2021162)

Physiologically based pharmacokinetic model for voriconazole in presence of liver impairment

ZHU Lina, DONG Ji, ZHENG Li   

  1. Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu, China
  • Received:2023-11-29 Revised:2024-03-20 Online:2024-11-26 Published:2024-10-24

摘要:

目的:预测不同程度肝损患者的伏立康唑药代动力学。方法:整合伏立康唑理化性质、体外数据及肝损患者的生理解剖数据,建立不同肝损程度的伏立康唑生理药动学模型,并用临床数据来验证该模型的准确性,预测不同程度肝损及不同CYP2C19基因型的患者伏立康唑药动学。结果:该生理药动学模型能准确预测不同程度肝损患者的伏立康唑药动学。结论:生理药动学模型可以准确评价肝损及代谢酶基因型对伏立康唑药动学的影响,为肝损患者的个体化用药提供支持。

关键词: 伏立康唑, 肝损, 生理药动学模型, 剂量调整

Abstract:

AIM: To predict voriconazole (VCZ)'s pharmacokinetics in patients with different degree of liver dysfunction. METHODS: The physiological based pharmacokinetics (PBPK) models were developed for VCZ based on drug's physico-chemical property and in-vitro data. Then liver dysfunction induced changes in physiological, anatomical parameter was integrated into the PBPK model. The clinical verified VCZ model was used to predict VCZ's PK in patients of different CYP2C19 genotype with different degree of liver dysfunction. RESULTS: The PBPK predicted the VCZ exposure in the patients with liver dysfunction with acceptable prediction error. CONCLUSION: The PBPK model developed here could evaluate the impact of liver dysfunction and CYP2C19 genotype on VCZ's pharmacokinetics and support individual dose adjustment of VCZ.

Key words: voriconazole, liver dysfunction, PBPK, dose adjustment

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