药物相互作用分析与复方药效模拟:一个方法学研究

An approach for the analysis of pharmacodynamic interactions and the simulation of combined response

目的基于正交设计,建立药效学相互作用分析方法和复方药效模拟方法。方法根据复方的组分数,从L8(23)、L8(24)、L12(25)和L12(26)中选用相应的正交设计;1水平为"使用",2水平为"不使用";用双向单侧t检验分析各组分在复方中的重要程度;提出了复方药效学模型和组分相互作用模型,用1个实例对此进行评价和考证;模拟偏倚由2种散点图结合评价。结果本法可确定各组分对复方药效的贡献值,排列其重要程度;给出配伍组相互作用性质(协同、拮抗、相加);建立的复方效应学模型,可对不同组合的复方进行药效模拟;2种散点视图评价预测的准确性。结论本法可提供丰富的组方信息,具有可行性和实用性,对3个以上组分的复方和临床研究更有价值。

Aim An approach is set up to study pharmacodynamic interaction and simulate the combined response.Methods An orthogonal design with 1-level=used and 2-level=not used,was selected from L8(23),L8(24),L12(25) and L12(26),and the two one-sided t tests was used to analyze the importance of component and its effectiveness.Some mathematical models were proposed to analyze drug interactions and to predict the combined response.The bias was evaluated by the both scatter plots.An example of the compound with six components was applied to evaluate this approach.Results This approach determined each component performance by its contribution to combined response,which showed the importance of a component in combination.Drug interactions were evaluated among the combinations in each group.The prediction model performed well and simulated the combined response in the different of components in combination.Conclusion The approach can provide more information about pharmacodynamic interactions than that from the analysis of variance,especially in clinical study and the compounds of more than 3 components.