Testing for synergism over a range of fixed ratio drug combinations: replacing the isobologram.

Tallarida RJ; Raffa RB

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Testing for synergism over a range of fixed ratio drug combinations: replacing the isobologram.

机译：测试一系列固定比例药物组合的协同作用：替换等效线图。

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An isobologram is a Cartesian plot of pairs of doses that, in combination, yield a specified level of effect. It is a convenient and presently popular way of graphically displaying results of drug-combination and similar studies, because paired values of experimental points that fall below or above the line connecting the axial points (usually ED50 values) denote supra- and sub-additive combinations, respectively. However, an isobologram does not fulfill the criteria for standard least squares regression analysis. It is thus less useful for addressing questions related to the range of combination ratios over which synergy occurs. We describe herein a substitute for the isobologram in which log(total-dose) is plotted against the proportion of a component in a combination. One advantage is that a nonlinear curve-fitting procedure and determination of the confidence interval of a single parameter allow the determination of departure from additivity over a range of fixed proportion mixtures. An example is given of the combination of two analgesics (acetaminophen and tramadol hydrochloride). Another advantage of the new method is the reduction of animal use.

机译：等效线图是剂量对的笛卡尔图，这些剂量对组合产生特定的作用水平。这是图形显示药物组合和类似研究结果的一种便捷且当前流行的方式，因为落在连接轴向点的线以下或之上的实验点的配对值（通常为ED50值）表示超加和亚加组合，分别。但是，等效线图不符合标准最小二乘回归分析的标准。因此，它对于解决与出现协同作用的组合比率范围有关的问题的用处不大。我们在这里描述了等效线图的替代物，其中对数（总剂量）相对于组合中组分的比例作图。一个优点是非线性曲线拟合程序和单个参数置信区间的确定允许确定在一定比例的混合物范围内与可加性的偏离。举两种止痛药（对乙酰氨基酚和盐酸曲马多）的组合为例。新方法的另一个优点是减少了动物的使用。

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《Life sciences》 |1996年第2期|共6页
作者
Tallarida RJ; Raffa RB;
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正文语种 eng
中图分类基础医学;
关键词
Drug Synergism; Pharmacology; 药物协同作用; 药理学;

机译：Drug Synergism;Pharmacology;药物协同作用;药理学;

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1. Testing for synergism over a range of fixed ratio drug combinations: replacing the isobologram. [J] . Tallarida RJ, Raffa RB Life sciences . 1996,第2期

机译：测试一系列固定比例药物组合的协同作用：替换等效线图。
2. Automatic Dissolution Testing with High-Temporal Resolution for Both Immediate-Release and Fixed-Combination Drug Tablets [J] . Zhongmei Chi, Irfan Azhar, Habib Khan, Scientific reports. . 2019,第1期

机译：用于立即释放和固定组合药片的高颞分辨率自动溶出试验
3. LARGE SAMPLE TESTS FOR BINARY OUTCOMES IN FIXED-DOSE COMBINATION DRUG STUDIES [J] . Wang SJ., Hung HMJ. Biometrics: Journal of the Biometric Society : An International Society Devoted to the Mathematical and Statistical Aspects of Biology . 1997,第2期

机译：固定剂量组合药物研究中二元结果的大样本测试
4. On Replacing Lagrange’s "Reduced Gradient Algorithm" by Simplified Fixed Point Iteration in Adaptive Model Predictive Control [C] . Hamza Khan, József K. Tar, Károly Széll IEEE International Conference on Intelligent Engineering Systems . 2019

机译：关于自适应模型预测控制中的简化定点迭代替换拉格朗日的“降低梯度算法”
5. Sample size determination for Emax model, equivalence/non-inferiority test and drug combination in fixed dose trials. [D] . Wang, Jie. 2008

机译：在固定剂量试验中确定Emax模型，等效性/非劣效性试验和药物组合的样本量。
6. Comparison of methodologies for synergism testing of drug combinations against resistant strains of Pseudomonas aeruginosa. [O] . D M Cappelletty, M J Rybak 1996

机译：药物组合对铜绿假单胞菌耐药菌株的协同测试方法学比较。
7. The thermodynamic changes that occur upon mixing five models of formamide and three models of water, including the miscibility of these model combinations itself, is studied by performing Monte Carlo computer simulations using an appropriately chosen thermodynamic cycle and the method of thermodynamic integration. The results show that the mixing of these two components is close to the ideal mixing, as both the energy and entropy of mixing turn out to be rather close to the ideal term in the entire composition range. Concerning the energy of mixing, the OPLS/AA-mod model of formamide behaves in a qualitatively different way than the other models considered. Thus, this model results in negative, while the other ones in positive energy of mixing values in combination with all three water models considered. Experimental data supports this latter behavior. Although the Helmholtz free energy of mixing always turns out to be negative in the entire composition range, the majority of the model combinations tested either show limited miscibility, or, at least, approach the miscibility limit very closely in certain compositions. Concerning both the miscibility and the energy of mixing of these model combinations, we recommend the use of the combination of the CHARMM formamide and TIP4P water models in simulations of water-formamide mixtures. [O] . Kiss, Bálint, Fábián, Balázs, Idrissi, Abdenacer, 2017

机译：通过使用适当选择的热力学循环和热力学积分方法进行蒙特卡罗计算机模拟，研究了将五种甲酰胺模型和三种水模型混合在一起时发生的热力学变化，包括这些模型组合本身的可混溶性。结果表明这两种组分的混合接近于理想的混合，因为混合的能量和熵在整个组成范围内都非常接近理想的项。关于混合的能量，甲酰胺的OPLS / AA-mod模型与其他模型相比，在质量上有不同的表现。因此，该模型得出的结果是负的，而其他模型则综合考虑了所有三个水模型的结果的正能量。实验数据支持后一种行为。尽管混合的亥姆霍兹自由能在整个组成范围内始终为负，但大多数测试模型组合显示出有限的混溶性，或至少非常接近某些组合物的混溶性极限。关于这些模型组合的可混溶性和混合能量，我们建议在水-甲酰胺混合物的模拟中使用CHARMM甲酰胺和TIP4P水模型的组合。

Testing for synergism over a range of fixed ratio drug combinations: replacing the isobologram.

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