Analysis of Drug Interactions
Analysis of Drug Interactions
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DOI：
10.1007/978-1-61779-080-5_34
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Peters, Godefridus J.
中科院分区：
文献类型：
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作者：
Bijnsdorp, Irene V.;Giovannetti, Elisa;Peters, Godefridus J.
目前大多数针对癌症的疗法，以及针对免疫疾病或病毒感染的疗法，由经验设计的组合策略组成，组合多种治疗剂。药物组合被广泛使用，因为多种药物影响多个靶点和细胞亚群。主要目的是相互增强治疗效果，而其他益处可能包括减少副作用和延迟或预防耐药性。绝大多数的联合治疗方案都是凭经验开发的，很少有实验研究旨在探索彻底不同的药物组合，使用适当的分析方法。然而，在临床前模型中可能的代谢和生物相互作用的模式的研究，以及调度，应改善大多数药物组合的发展。协同作用的定义是组合比单独的每种药剂更有效，例如，其中一种药剂增强第二种药物的作用。拮抗作用的定义是组合比单一药剂更不有效，例如一种药剂抵消另一种药剂的作用。可以通过以各种不同的方式组合两种药剂来研究组合，例如同时或顺序组合方案。在临床评估之前，必须测试组合的效力，以防止拮抗作用。然而，人们应该认识到，当涉及毒性时，可能需要拮抗作用，即一种药物降低另一种药物的副作用。已经进行了几次尝试来定量测量每种药物单独及其组合的剂量-效应关系，并确定给定的组合是否会获得协同效应。评价联合用药是否有效的最广泛使用的方法之一是中位药物效应分析法。使用该方法，从药物细胞毒性或生长抑制曲线计算组合指数（CI）。为了计算CI，可以使用计算机软件Calcusyn，考虑生长抑制曲线的整个形状来计算组合是协同的、相加的还是拮抗的。在这里，我们描述了如何在体外设计组合，以及如何使用Calcusyn或Compusyn分析它们。此外，陷阱，限制，和使用这些组合和Calcusyn/Compusyn的优点进行了描述。
Most of the current therapies against cancer, and also those against immune diseases or viral infections, consist of empirically designed combination strategies, combining a variety of therapeutic agents. Drug combinations are widely used because multiple drugs affect multiple targets and cell subpopulations. The primary aim is a mutual enhancement of the therapeutic effects, while other benefits may include decreased side effects and the delay or prevention of drug resistance. The large majority of combination regimens are being developed empirically and there are few experimental studies designed to explore thoroughly different drug combinations, using appropriate methods of analysis. However, the study of patterns of possible metabolic and biological interactions in preclinical models, as well as scheduling, should improve the development of most drug combinations. The definition of synergism is that the combination is more effective than each agent separately, e.g., one of the agents augments the actions of the second drug. The definition of antagonism is that the combination is less effective than the single agents, e.g. one of the agents counteracts the actions of the other. A combination can be studied by combining the two agents in various different ways, such as simultaneous or sequential combination schedules. It is essential to test the potency of a combination, before evaluation in the clinic, to prevent antagonistic actions. However, one should realize that an antagonistic action may be desired when toxicity is concerned, i.e. one drug decreases the side effects of another drug. Several attempts have been made to quantitatively measure the dose-effect relationship of each drug alone and its combinations and to determine whether a given combination would gain a synergistic effect. One of the most widely used ways to evaluate whether a combination is effective is the median-drug effect analysis method. Using this method, a combination index (CI) is calculated from drug cytotoxiciry or growth inhibition curves. To calculate a CI, the computer software Calcusyn can be used, taking the entire shape of the growth inhibition curve into account for calculating whether a combination is synergistic, additive, or antagonistic. Here, we describe how combinations can be designed in vitro and how to analyze them using Calcusyn or Compusyn. Moreover, pitfalls, limitations, and advantages of using these combinations and Calcusyn/Compusyn are described.