Vogel G
Arzneimittelforschung. 1975 Sep;25(9):1356-65.
The following experiments were carried out on the question of the "predictability" of the effect of drug combinations. A methanol extract from Viscum album causes a rise in coronary perfusion in isolated and perfused (Langendorff's method) guinea pig hearts. Administration of a methanol extract from Crataegus oxyacantha results not only in a rise in coronary perfusion, but also in a positive inotropic effect. Combined application of the drugs leads to a pure addition of effects, which are therefore "predictable". Extracts from Rhamnus frangula, Rheum sinens. and Senna lead to a dose-dependent reduction in the gastro-intestinal passage time. Combining the three extracts results in a pure addition of the effects. An extract from Potentilla anserina, which when given alone lengthens the gastrointestinal passage time, antagonises the laxative effect of extracts from Rheum sinens., Rhamnus frangula and Senna. All the effects we tested in the area of the gastro-intestinal tract behaved in a purely additive way and were therefore "predictable". When given separately the ethereal oils menthol, oleum juniperi, borneol and eugenol as well as dehydrocholic acid-Na-salt and alpha-naphthyl acetic acid-Na-salt cause, in rats, a dose-dependent increase in bile flow. Combining two or three of these substances results in a pure addition of the effects. The effects of all the test substances were therefore "predictable". When given separately valepotriate, morphine, scopolamine, ajmalicine, rescinnamine, reserpinine and reserpine, as depressants of the central nervous system (CNS), lead to a dose-dependent lengthening of hexobarbital-induced sleeping time in mice. However, when combined, these substances lead to a lengthening of hexobarbital sleeping time which is well above what was to be expected following application of the single substances. So, it can happen that the combination of the two single doses which, when taken separately produce no effect, leads to a lengthening of hexobarbital-induced sleeping time by more than 100 percent. In the case of CNS depressants, it is therefore true to say that their effect, when given in combination, was "unpredictable". It can be seen from these findings that, at least in the case of the tested extracts and single substances, which are all of plant origin, the "predictability" of the effect of the test substances in combination is the rule, and the "unpredictability" the exception. In addition the investigations may give further information concerning the methods as to how the question of "predictability" can be studied experimentally.
针对药物组合效果的“可预测性”问题进行了以下实验。欧洲槲寄生的甲醇提取物可使离体灌流（Langendorff法）豚鼠心脏的冠脉灌注增加。山楂的甲醇提取物给药后不仅会使冠脉灌注增加，还会产生正性肌力作用。两种药物联合应用会使效果单纯相加，因此是“可预测的”。鼠李、大黄和番泻叶的提取物会使胃肠道通过时间呈剂量依赖性缩短。三种提取物联合应用会使效果单纯相加。鹅绒委陵菜的提取物单独使用时会延长胃肠道通过时间，它能拮抗大黄、鼠李和番泻叶提取物的导泻作用。我们在胃肠道领域测试的所有效果都呈单纯相加的方式，因此是“可预测的”。薄荷脑、杜松子油、冰片和丁香酚等挥发油以及脱氢胆酸钠和α-萘乙酸钠单独给大鼠用药时会使胆汁流量呈剂量依赖性增加。将其中两种或三种物质联合应用会使效果单纯相加。因此，所有受试物质的效果都是“可预测的”。缬草三酯、吗啡、东莨菪碱、阿吗灵、利血胺、利血平宁和利血平作为中枢神经系统（CNS）抑制剂单独给小鼠用药时，会使戊巴比妥诱导的睡眠时间呈剂量依赖性延长。然而，联合应用时，这些物质会使戊巴比妥睡眠时间延长，远远超过单独应用各单一物质时预期的延长时间。所以，可能会出现这样的情况：两种单独使用时无作用的单剂量药物联合应用会使戊巴比妥诱导的睡眠时间延长超过100%。因此，就中枢神经系统抑制剂而言，确实可以说它们联合应用时的效果是“不可预测的”。从这些研究结果可以看出，至少在所测试的均为植物来源的提取物和单一物质的情况下，受试物质联合应用效果的“可预测性”是普遍规律，而“不可预测性”是例外情况。此外，这些研究可能会就如何通过实验研究“可预测性”问题的方法提供更多信息。
