Pöch G, Dittrich P, Reiffenstein R J, Lenk W, Schuster A
Institute of Pharmacodynamics and Toxicology, University of Graz, Austria.
Can J Physiol Pharmacol. 1990 Oct;68(10):1338-45. doi: 10.1139/y90-202.
Dose-frequency curves of toxic effects of a substance A were evaluated in the absence and in the presence of a fixed dose of a second substance B. Data were fitted by the curve-fitting program ALLFIT. Observed combined frequencies of A + B were compared statistically with the expected frequencies of additivity and (or) independence by the phi 2-square goodness-of-fit test. The theoretical dose-frequency curves expected for an additive response were obtained by a solely graphical procedure and the theoretical curves for independent effects were calculated from the effects of B and A at certain doses. In rotarod tests with trained mice, the combined deteriorating effect of ethanol and benzodiazepines were significantly over-additive. However, their lethal interaction appeared underadditive in mice. The lethal underadditive interaction of ethanol and phencyclidine (PCP) can be ascribed largely to independent actions of these compounds. Loss of righting reflex was additively enhanced by PCP, whereas PCP overadditively enhanced the effect of ethanol. The insecticidal action of the cholinesterase inhibitors malathion and parathion appeared additive and significantly different from independent interaction. A comparison of results from dose-response curves with isoboles showed good agreement. The method appears as an attractive alternative or as a complementary procedure to the isobolographic analysis. Combination experiments as described can be carried out and evaluated rather simply, with a minimum of expenditure and a maximum of information.
在不存在和存在固定剂量的第二种物质B的情况下，评估了物质A的毒性作用的剂量-频率曲线。数据由曲线拟合程序ALLFIT进行拟合。通过phi 2平方拟合优度检验，将观察到的A + B的联合频率与预期的相加和（或）独立频率进行统计学比较。通过单独的图形程序获得相加反应预期的理论剂量-频率曲线，并根据B和A在特定剂量下的作用计算独立作用的理论曲线。在对训练过的小鼠进行的转棒试验中，乙醇和苯二氮卓类药物的联合恶化作用明显超过相加作用。然而，它们在小鼠中的致死相互作用似乎低于相加作用。乙醇和苯环利定（PCP）的致死性低于相加相互作用很大程度上可归因于这些化合物的独立作用。PCP相加性增强了翻正反射丧失，而PCP超相加性增强了乙醇的作用。胆碱酯酶抑制剂马拉硫磷和对硫磷的杀虫作用表现为相加作用，且与独立相互作用有显著差异。剂量-反应曲线与等效线图的结果比较显示出良好的一致性。该方法似乎是等效线图分析的一种有吸引力的替代方法或补充程序。所述的联合实验可以相当简单地进行和评估，花费最少且信息最多。
