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中国临床药理学与治疗学 ›› 2023, Vol. 28 ›› Issue (11): 1275-1282.doi: 10.12092/j.issn.1009-2501.2023.11.010

• 综述与讲座 • 上一篇    下一篇

群体模型分析方法评估基因多态性对药物PK/PD的影响

刘 璐1,石雨菲1,何庆烽1,徐凤艳2,王 鲲2,蔡卫民1,相小强1   

  1. 1复旦大学药学院临床药学与药事管理系,上海  200032;2上海强世信息科技有限公司,上海  200032
  • 收稿日期:2022-10-28 修回日期:2023-05-23 出版日期:2023-11-26 发布日期:2023-11-10
  • 通讯作者: 相小强,男,教授,研究方向:定量药理学。 E-mail: xiangxq@fudan.edu.cn
  • 作者简介:刘璐,女,博士,研究方向:定量药理学。 E-mail: lucy.liu@shcscc.com
  • 基金资助:
    国家自然科学基金项目(81973389,82011540409)

Application of population modeling analysis to evaluate the impact of gene polymorphism on drug PK/PD 

LIU Lu1, SHI Yufei1, HE Qingfeng1, XU Fengyan2, WANG Kun2, CAI Weimin1, XIANG Xiaoqiang1   

  1. 1 Department of Clinical Pharmacy, School of Pharmacy, Fudan University, 2 Shanghai Qiangshi Information Technology Co., Ltd, Shanghai 200032, China
  • Received:2022-10-28 Revised:2023-05-23 Online:2023-11-26 Published:2023-11-10

摘要:

多态性(polymorphism)是指在一个生物群体中,同时和经常存在两种或多种不连续的变异型或基因型(genotype)或等位基因(allele),亦称遗传多态性或基因多态性(gene polymorphism)。这种基因多态性可能对药物的药动学和药效学产生一定程度的影响。基因组学的研究对实现个性化、以患者为导向的精准医学治疗方式具有重要作用。群体模型分析是采用模型化的方法来定量描述药动学及药效学参数与个体特征之间的相关性和变异性,可以量化协变量产生的影响。目前这一方法已被广泛应用。本文系统地介绍采用群体模型方法评估基因多态性对药物PK/PD影响的应用实例。

关键词: 定量药理学, 基因多态性, 群体药动学

Abstract:

Polymorphism refers to the simultaneous and frequent existence of two or more discontinuous variants or genotypes or alleles in a biological population, also known as genetic polymorphisms or genes Polymorphism. This gene polymorphism may have a certain degree of influence on the pharmacokinetics and pharmacodynamics of the drug. The study of genomics plays an important role in realizing personalized, patient-oriented precision medicine treatment. Population model analysis is to use a modeling method to quantitatively describe the correlation and variability between pharmacokinetic and pharmacodynamic parameters and individual characteristics and to quantify the impact of covariates. At present, this method has been widely used. This paper systematically introduces the application examples of using the population model approach to assess the effects of genetic polymorphisms on the drug PK/PD.

Key words: quantitative pharmacology, genetic polymorphism, population pharmacokinetics

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