A DIRECT, GENERAL-APPROACH BASED ON ISOBOLOGRAMS FOR ASSESSING THE JOINT ACTION OF DRUGS IN PRECLINICAL EXPERIMENTS
A DIRECT, GENERAL-APPROACH BASED ON ISOBOLOGRAMS FOR ASSESSING THE JOINT ACTION OF DRUGS IN PRECLINICAL EXPERIMENTS
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DOI：
10.1002/sim.4780132202
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发表时间：
1994-11-30
影响因子：
2
通讯作者：
ROBINSON, GA
中科院分区：
文献类型：
--
作者：
MACHADO, SG;ROBINSON, GA
药理学家和其他生物学家经常使用基于等效线图解释的方法来量化临床前研究中联合使用的药物之间的协同作用或拮抗作用的程度。从统计学的观点来看，大多数方法都不令人满意，许多是因为它们仅仅依赖于视觉评价，其他方法则是因为这些方法没有考虑到测量的可变性。我们描述了一种直接的方法，用于量化两种药物的联合效力，一个中心特征是使用简单的等效线模型，直接导致预期的实验结果的响应面模型。该方法是通用的，因为它可以用于离散或连续的反应，不同的潜在概率分布，单独使用的药物的线性或非线性剂量反应函数，以及各种实验设计。我们的方法扩展了Hewlett提出的测量药物联合效力的建议，并且在精神上类似于Greco等人和Weinstein等人提出的方法。我们描述了对体外实验数据的分析，该实验是为了评价抗病毒药物AZT和ddI联合使用的功效而进行的。
Pharmacologists and other biologists frequently use methods based on the interpretation of isobolograms to quantify the extent of synergy or antagonism between drugs used in combination in pre-clinical studies. Most methods have been unsatisfactory from a statistical viewpoint, many because they have relied solely on visual evaluation, others because the methods have not taken into account the variability of the measurements. We describe a direct approach for quantifying the joint potency of two drugs, a central feature being the use of simple isobole models that lead directly to response surface models for the expected experimental outcomes. The approach is general in the sense that one can use it for discrete or continuous responses, different underlying probability distributions, linear or non-linear dose-response functions of the drugs used singly, and a variety of experimental designs, Our approach extends the suggestions made by Hewlett for measuring the joint potency of drugs, and is similar in spirit to the approaches proposed by Greco ef al. and Weinstein et al. We describe the analysis of data from an in vitro experiment conducted to evaluate the efficacy of the antiviral drugs AZT and ddI used in combination.