摘要
背景:分析互动药物常用的方法(如协同、拮抗作用)如法,结合指数和曲线的移动是基于LoeweAdditivity原则乐的剂量当量和类似的浓度-效应的内在假设(英)包括平行曲线和平等的影响最大(Emax),因此不适合药物与迪斯类似的c-e.这项研究描述了一种新的方法,是没有这种限制,使统计分析的额外优势。 方法和结果:该方法包括两个步骤。首先,在剂量当量原理的基础上,利用实验获得的一种药物的汉英对照,计算出该药的等效有效成分。其他药物在没有交互性的情况下,由此产生的20个相互作用的汉英形成可加性信封的上下界。接下来,从实验数据计算出95%置信区间。在加性包络中加入不确定包络(UE)。实验观察到的药物组合的影响(c-ecomb,观察)位于UE表明相加而c-ecomb,OBS到上方或下方显示有统计学意义(P<UE 0.05)的协同或拮抗作用,分别。在硅片上的额外研究证明了可加性信封的形状和大小。我决定来检测药物交互的能力,取决于药物浓度比和他们对汉英曲线形状参数的比值。对实验结果分析的结合与平行的英和/或不平等的Emax表示UE更灵活,提供了更多的药物信息,相比以前的方法。 结论:UE分析广泛适用的方法,包括统计意义的评估,药物性。
关键词: 联合治疗,药物的交互性,LoeweAdditivity,不确定性的信封,显著的协同作用,拮抗作用。
Current Cancer Drug Targets
Title:Method to Assess Interactivity of Drugs with Nonparallel Concentration Effect Relationships
Volume: 17 Issue: 8
关键词: 联合治疗,药物的交互性,LoeweAdditivity,不确定性的信封,显著的协同作用,拮抗作用。
摘要: Background: Commonly used methods for analyzing interactivity between drugs (e.g. synergy, antagonism) such as isobologram, combination index, and curve shift are based on the Loewe Additivity principle of dose equivalence and the inherent assumption of similar concentration- effect (C-E) including parallel curves and equal maximum effects (Emax), and therefore are not suitable for drugs with dissimilar C-E. This study describes a new method that is without this limitation and has the additional advantage of enabling statistical analysis.
Methods and Results: The method comprises two steps. First, based on the dose equivalence principle, the experimentally obtained C-E of one drug was used to calculate the equally effective C-E of the other drug at no interactivity; the resulting two zero-interactivity C-E formed the upper and lower boundaries of Additivity Envelope. Next, 95% confidence intervals calculated from experimental data were added to Additivity Envelope to obtain Uncertainty Envelope (UE). Experimentally observed effects of drug combinations (C-Ecomb,observed) located within UE indicate additivity whereas C-Ecomb,observed located above or below UE indicate statistically significant (p<0.05) synergy or antagonism, respectively. Additional in silico studies demonstrated the shape and size of Additivity Envelope, which determines the ability to detect drug interactivity, depended on the Drug A-to-B concentration ratios and the ratios of their C-E curve shape parameter. Analyses of experimental results of combinations of drugs with nonparallel C-E and/or unequal Emax indicated UE as more versatile and provided more information, compared to earlier methods.
Conclusion: UE is a broadly applicable method for analysis, including statistical significance assessment, of drug interactivity.
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Cite this article as:
Method to Assess Interactivity of Drugs with Nonparallel Concentration Effect Relationships, Current Cancer Drug Targets 2017; 17 (8) . https://dx.doi.org/10.2174/1568009617666170330154054
DOI https://dx.doi.org/10.2174/1568009617666170330154054 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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