Drugs which independently inhibit a shared target or pathway can have synthetic activities that result in multiplicative instead of merely additive potencies. This characteristic of drug combinations can be quantified by expressing the potency of the combination as if it were a single agent. We show that by optimizing this quantity we can prospectively design drug cocktails with apparent potencies that far exceed any of its individual components. We illustrate the power of this approach, which is based on statistical design of experiments to select optimal drug combinations, and response surface methodology to determine optimal drug ratios, by building a drug cocktail comprised of three antibodies for treating C. difficile infection that is almost 1000-fold more potent than the current, clinically approved antibody monotherapy. High synthetic activities do not require unusual drug interactions, and therefore may be achievable much more readily than generally appreciated.

中文翻译：

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利用合成活性设计超强效抗体混合物

独立抑制共同靶点或途径的药物可以具有合成活性，从而产生乘法而不是仅仅加法效力。药物组合的这种特性可以通过表达组合的效力来量化，就好像它是单一药剂一样。我们表明，通过优化这一数量，我们可以前瞻性地设计出药效远远超过其任何单个成分的药物鸡尾酒。我们说明了这种方法的力量，该方法基于实验的统计设计来选择最佳药物组合，以及通过构建由三种抗体组成的药物混合物来确定最佳药物比例的响应面方法来治疗艰难梭菌。这种感染比目前临床批准的抗体单一疗法强近 1000 倍。高合成活性不需要不寻常的药物相互作用，因此可能比一般认为的更容易实现。