多药合用药效学协同、相加和拮抗定量计算新方法的建立

发布时间：2018-05-22 15:30

本文选题：多药合用 + 药物相互作用　；参考：《中国药理学与毒理学杂志》2016年12期

【摘要】：许多严重疾病如癌症的病因复杂,属于多靶点疾病,针对多个靶点联合用药比单靶点用药更容易实现治疗目的。药物联用可产生多层面的相互作用,最终表现为药效发生协同、相加或拮抗。对其进行定量评价的前提是获得多药合用组合的预期相加效应值。但长期以来一直缺乏精确计算协同、相加和拮抗的可靠方法,使新复方药物研究等发展受阻。通过等效剂量兑换和引入药理学中的药效的序贯和集合原理,作者发现了多药合用组合预期相加效应的数学规律,简述如下:多药合用剂量组合的预期相加效应值是一个连续的数值范围,即预期相加效应值是药物组合剂量的闭区间数集函数,建立了通用型计算公式。在二维坐标系中显示为一条量效曲带,与多药合用组合的实际量效曲线构成一幅"一条曲带和一条曲线"的图像。组成预期相加量效曲带的量效曲线的数量,随着合用药物数量的增加呈指数性增长。通过计算实际量效曲线和相加量效曲带的交点坐标,能够得出多药合用组合药效发生协同、相加或拮抗的剂量范围;通过比较实际量效曲线中的效应值(或剂量值)与相加量效曲带的偏离状况,能够得出发生协同、相加或拮抗程度的指标,如剂量合用指数和效应合用指数等。该方法能为新复方药物研发、多药联合效应的定量评价和中药复方的效应评价等提供可靠通用的计算方法,简称为"一带一线"法。
[Abstract]:Many serious diseases such as cancer have complicated etiology and belong to multi-target diseases. A combination of drugs can produce multiple-level interactions that ultimately result in synergistic, additive or antagonistic effects. The premise of quantitative evaluation is to obtain the expected additive effect of multidrug combination. However, for a long time, there is a lack of reliable methods of accurate calculation, addition and antagonism, which impedes the development of new compound drugs. By equivalent dose exchange and the sequential and collective principle of pharmacological efficacy, the authors found the mathematical law of the expected additive effect of multidrug combination. The results are summarized as follows: the expected additive effect of multidrug combination dose combination is a continuous numerical range, that is, the expected additive effect value is a set function of closed interval number of drug combination dose, and a general calculation formula is established. In a two-dimensional coordinate system, a quantitative curved band is displayed, and the actual volume effect curve combined with multiple drugs constitutes an image of "one curved band and one curve". The number of dose-response curves composed of the expected additive effect curve increased exponentially with the increase of the amount of combined drugs. By calculating the coordinate of the intersection point between the actual dose effect curve and the additive effect curve, the dose range of synergistic, additive or antagonistic effect of multi-drug combination can be obtained. By comparing the deviation between the effect value (or dose value) in the actual dose-effect curve and the additive effect curve, the indexes of synergistic, additive or antagonistic degree, such as dose combination index and effect combination index, can be obtained. This method can provide a reliable and general calculation method for the research and development of new compound drugs, quantitative evaluation of multi-drug combination effect and effect evaluation of traditional Chinese medicine compound.
【作者单位】：军事医学科学院放射与辐射医学研究所药物毒理与肿瘤药理实验室;
【分类号】：R96

【相似文献】