几种常用药物联用计算方法的数学瑕疵和一带一线模型法的解决方案

doi:10.19803/j.1672-8629.2021.01.03

中国药物警戒 ›› 2021, Vol. 18 ›› Issue (1): 11-17.
DOI: 10.19803/j.1672-8629.2021.01.03

• 复方与联合用药安全性评价专栏(第一辑) • 上一篇下一篇

几种常用药物联用计算方法的数学瑕疵和一带一线模型法的解决方案

袁守军

军事医学研究院辐射医学研究所药物研究室,北京 100850

收稿日期:2020-09-18 修回日期:2021-01-18 出版日期:2021-01-15 发布日期:2021-01-18
作者简介:袁守军,男,研究员·博导,定量药理学与肿瘤药理学。

Mathematical Flaws of Commonly Used Calculating Methods of Multi-drug Combination and Solution Based on One Belt and One Line Model Method

YUAN Shoujun

Department of Drugs,Beijing Institute of Radiation Medicine,Academy of Military Medical Sciences,Beijing 100850,China

Received:2020-09-18 Revised:2021-01-18 Online:2021-01-15 Published:2021-01-18

摘要/Abstract

摘要： 多药联用在临床实践中很常见,药物间的相互作用会使药物效应发生改变,联用组合有可能使疗效增加和毒性减少,也有可能会带来药效降低和毒性增大的风险。已有多种计算方法用于定量评价药物联用产生的协同、相加和拮抗,但业内所用的许多计算方法均为共识性方法或经验公式,同一组数据用不同的方法处理,常会得出不同的、相互矛盾的结论。本文用数学方法分析了业内常用的几种计算方法的瑕疵,包括:Loewe等效线法、Bliss独立模型法、周氏中效法和金氏法等,并通过介绍本实验室发现的药物联用药效相加的数学规律,发展了具有自主知识产权的一带一线模型法,作为解决多药联用效应定量评价的通用方案,为充分体现多药联用带来的益处和规避多药联用带来的疗效和毒性风险提供可靠的计算方法。

关键词: 多药联用, 药物相互作用, 定量评价, 协同, 相加, 拮抗, 预期相加效应, 量效曲带, 一带一线模型

Abstract: Multi-drug combination is very common in clinical settings of refractory diseases.The multi-level interactions between drugs will make difference to the efficacy of drugs,as drug combinations may either increase the efficacy and reduce the toxicity or bring the risk of decreased efficacy and increased toxicity.There are a number of calculation methods for quantitative evaluation of the synergy,addition and antagonism of multi-drug combination.However,many of the methods used in this industry are all consensus methods or empirical formulas,so that the same set of data is processed by different methods,and different and contradictory conclusions often arise.In this paper,we used mathematical methods to analyze the flaws of several commonly used calculation methods in the industry,including Loewe's equivalent line method,Bliss's independent model method,Chou's median effect method and Jin's method.And by introducing the mathematical law of efficacy addition in multi-drug combination found in our laboratory,we established a one-belt and one-line model,which can be used as a universal and reliable method for quantitative evaluation of efficacy in multi-drug combination,which is expected to help to fully uncover the benefits of multi-drug combination and minimize the risk of efficacy reduction and toxicity enhancement.

Key words: multi-drug combination, drug interaction, quantitative evaluation, synergism, addition, antagonism, expected additive effect, dose-effect belt, one-belt and one-line model

中图分类号:

R288R969.3

袁守军. 几种常用药物联用计算方法的数学瑕疵和一带一线模型法的解决方案[J]. 中国药物警戒, 2021, 18(1): 11-17.

YUAN Shoujun. Mathematical Flaws of Commonly Used Calculating Methods of Multi-drug Combination and Solution Based on One Belt and One Line Model Method[J]. Chinese Journal of Pharmacovigilance, 2021, 18(1): 11-17.

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几种常用药物联用计算方法的数学瑕疵和一带一线模型法的解决方案

Mathematical Flaws of Commonly Used Calculating Methods of Multi-drug Combination and Solution Based on One Belt and One Line Model Method

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