Efficient designs for studying synergistic drug combinations
Efficient designs for studying synergistic drug combinations
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DOI：
10.1016/s0024-3205(97)01030-8
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发表时间：
1997-11-21
期刊：
影响因子：
6.1
通讯作者：
Raffa, RB
中科院分区：
文献类型：
--
作者：
Tallarida, RJ;Stone, DJ;Raffa, RB
区分药理学相加和协同药物组合需要实验设计和统计分析，这通常需要大量的动物和大量的实验时间。目前的研究采用了一种设计，将每种药物的单独剂量效应数据转化为固定药物比例的理论上的加和总剂量组合，以产生复合加和剂量效应关系，可以与具有相同比例的实际混合物进行比较。这种方法结合使用鞘内剂量的吗啡和可乐定，得到的结果实际上与使用相同数据集的等辐射线分析得到的结果相同。两项分析均显示该组合具有显着的协同作用，并且在每种方法中，无需将药物回归线限制为平行。与 isobole 方法相比，使用复合加性剂量效应关系还可以观察一系列效应的相互作用，同时减少所需数据集的大小。 (C) 1997 爱思唯尔科学公司。
Distinguishing between pharmacologically additive and synergistic drug combinations requires experimental designs and statistical analyses that often require appreciable numbers of animals and much experimenter time. The current study employed a design in which individual dose-effect data from each drug were translated into theoretically additive total dose combinations, in a fixed drug proportion, in order to produce a composite additive dose-effect relation that could be compared with that of an actual mixture having the same proportion. Results from this approach, using a combination of intrathecal doses of morphine and clonidine, were virtually identical to those using isobolographic analysis of the same data set. Both analyses showed significant synergism for this combination and, in each method, it was not necessary to constrain the drug regression lines to parallelism. In contrast to the isobole approach, the use of the composite additive dose-effect relation also allows observation of the interaction over a range of effects while reducing the size of the data sets needed. (C) 1997 Elsevier Science Inc.