Gori E, Visconti A, Sangiovanni M, Alieri U, Scrollini F
Quad Sclavo Diagn. 1979 Jun;15 Suppl 1:532-79.
In the introductory part a new classification of joint drug actions is submitted, according which three fundamental types are distincted, named respectively interference, cooperation and true interaction. In its turn, interaction is subdivided in three classes (uni-effectual, bis-ineffectual, bis-effectual) in the last of which is placed the most relevant of the interactions, that is synergism, subclassified, at its turn, as additive, super and infra-additive. The second part is devoted to the classification of the bacteriological techniques hitherto proposed in order to evaluate in vitro and in vivo the antibacterial interaction of chemoantibiotics. The third part is devoted to the classification and critical analysis of biometrical techniques hitherto applied to above quoted bacteriological techniques in order to obtain a quantitative evaluation of interaction. Criticism versus isobolic model is pointed out. In the final part a new procedure, named isoeffectual, is proposed. According to such a procedure a close grid of single and joint concentrations of a couple of chemoantibiotics, broad enough in order to cover the whole of the effects to be explored, is tested in vitro adopting the one-center agar diffusion test or a liquid medium. The experimental data so obtained are related in a planar diagram to the log of the sum obtained by adding to the concentrations of the first the concentrations of the second agent, converted into equi-effectual concentrations of the first. By this way a series of curvilinear regressions is obtained, which may be all explained by a mathematical formula according which the data may be submitted to statistical analysis and elaborated in order to draw the parameters able to define quantitatively the interaction. The model so applied is discussed as a general model for joint drug action.
在引言部分,提出了一种联合药物作用的新分类方法,据此区分出三种基本类型,分别称为干扰、协同和真正的相互作用。相互作用又依次细分为三类(单效、双无效、双效),其中最相关的相互作用即协同作用被归入最后一类,协同作用又依次细分为相加、超相加和亚相加。第二部分致力于对迄今提出的用于体外和体内评估化学抗生素抗菌相互作用的细菌学技术进行分类。第三部分致力于对迄今应用于上述细菌学技术以获得相互作用定量评估的生物统计学技术进行分类和批判性分析。指出了对等效应线模型的批评。在最后一部分,提出了一种名为等效应的新方法。根据该方法,采用单中心琼脂扩散试验或液体培养基在体外测试一对化学抗生素的单一和联合浓度的紧密网格,其范围足够宽以涵盖所有要探索的效应。如此获得的实验数据在平面图中与通过将第二种药物的浓度转换为第一种药物的等效浓度后加到第一种药物的浓度上所得到的和的对数相关。通过这种方式获得了一系列曲线回归,所有这些回归都可以用一个数学公式来解释,根据该公式,数据可以进行统计分析和处理,以得出能够定量定义相互作用的参数。所应用的模型作为联合药物作用的通用模型进行了讨论。