THE EXPECTED EFFECT OF A COMBINATION OF AGENTS - THE GENERAL-SOLUTION
THE EXPECTED EFFECT OF A COMBINATION OF AGENTS - THE GENERAL-SOLUTION
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DOI：
10.1016/s0022-5193(85)80176-4
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发表时间：
1985-01-01
影响因子：
2
通讯作者：
BERENBAUM, MC
中科院分区：
文献类型：
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作者：
BERENBAUM, MC
药剂之间的相互作用(药物、致癌物质、生理刺激、环境污染物等)它们的作用在生物学和医学的几乎每一个分支中都具有根本的兴趣和实际的重要性。当药物组合的作用大小大于或小于预期时，就说药物组合表现出相互作用，期望是基于组合中各个药物的剂量-效应关系。问题的关键是决定预期是什么，为此提出了各种规则(例如，预期效果是组合的各个组成部分的影响的总和，或者是这些影响的乘积，或者它可以从质量作用定律计算出来)。这些规则对于具有特定和相当受限类型的剂量-效应关系的药物组合是有效的，但它们没有普遍的有效性。这里给出了这个问题的一般解决方案，它使得非交互组合的效果可以直接根据单个药剂的剂量-效应关系(无论是用代数还是用数字表示)来计算，而不考虑所涉及的特定类型的剂量-效应关系。该解决方案基于这样一个事实，即当由n个不相互作用以产生该效果的药剂组合产生特定大小的效果时，表示由各个药剂的剂量轴所跨越的n维空间中的组合的点与表示与其等效性和等效量的个别药剂的其他组合的点位于相同的(n-1)维超平面中。通过将这一一般原理应用于特定类型的剂量-效应关系，可以推导出计算非相互作用组合的效果的方法，作为其成分的效果的总和或乘积，或根据质量作用定律，每种方法在适当的情况下都是正确的(而不援引作用机制)。
Interactions between agents (drugs, carcinogens, physiological stimuli, environmental pollutants, etc.) in producing their effects are of fundamental interest and practical importance in virtually every branch of biology and medicine. A combination of agents is said to show interaction when the magnitude of its effect is greater or smaller than expected, expectation being based on the dose-effect relations of the individual agents in the combination. The crux of the matter is to decide what is expected, and various rules have been proposed to this end (for example, that the expected effect is the sum of the effects of the individual constituents of the combination, or that it is the product of these effects, or that it may be calculated from the law of mass action). These rules are valid for combinations of agents with particular and rather restricted types of dose-effect relations, but they have no general validity. A general solution to this problem is given here, that enables the effects of noninteractive combinations to be calculated directly from the dose-effect relations of the individual agents (whether expressed algebraically or numerically), regardless of the particular types of dose-effect relations involved. This solution is based on the fact that when an effect of particular magnitude is produced by a combination of n agents which do not interact to produce that effect, the point representing the combination in the n-dimensional space spanned by the dose-axes of the individual agents lies in the same (n-1)-dimensional hyperplane as those representing other combinations isoeffective with it and isoeffective amounts of the individual agents. Methods for calculating the effect of a noninteractive combination as the sum or product of the effects of its constituents, or from the law of mass action, each of which is correct in appropriate cases, may be deduced (without invoking mechanisms of action) by applying this general principle to particular types of dose-effect relations.