Isobolographic analysis for combinations of a full and partial agonist: Curved isoboles
Isobolographic analysis for combinations of a full and partial agonist: Curved isoboles
复制标题
DOI：
10.1124/jpet.104.067264
复制
发表时间：
2004-09-01
影响因子：
3.5
通讯作者：
Tallarida, RJ
中科院分区：
文献类型：
--
作者：
Grabovsky, Y;Tallarida, RJ
治疗上经常使用药物组合来达到增强的效果，而无需使用过量的任何一种药物。如果药物发挥明显相似的作用，例如。例如，两种镇痛药，可以测试组合的效果的加和性，即基于单独药物效力实现的效果水平。但激动剂的组合有时会表现出超加性（协同）或亚加性反应。无论这两种激动剂都是药物，还是药物和内源性化学物质的组合，人们都对表征相互作用以确定其是否偏离加和性感兴趣，因为这种定量信息除了其治疗重要性之外，还可能阐明机制。这种表征的常用方法是使用等效线图。这是产生相同效果水平（通常取最大值的 50%）的剂量组合（a、b）的直角坐标图。在其通常的形式中，该图被构造为连接代表单独有效剂量的截距的直线（可加性），例如。例如，每个的ED50值。当测试的组合在这条线上或线外时，这条线是区分加性与非加性相互作用的参考。这里讨论的是该线性图背后的假设。具体来说，我们表明，具有可变效力比的药物组合（以完全激动剂和部分激动剂为例）会导致加和性的曲线等值线，该等值线可能被错误地归因于协同作用或次加和性。
Combinations of drugs are frequently used therapeutically to achieve an enhanced effect without using an excess quantity of either agent. If the drugs exert overtly similar action, e. g., two analgesics, the effect of the combination may be tested for additivity, i.e., an effect level that is achieved based on the individual drug potencies. But combinations of agonists will sometimes display either superadditive ( synergistic) or subadditive responses. Whether the two agonists are both drugs, or a combination of a drug and an endogenous chemical, there is interest in characterizing the interaction to determine whether it departs from additivity because quantitative information of this kind, aside from its therapeutic importance, may also illuminate mechanism. A common method for this characterization uses the isobologram. This is a plot in rectangular coordinates of dose combinations (a, b) that produce the same effect level ( often taken to be 50% of the maximum). In its usual form, this plot is constructed as a straight line ( of additivity) connecting intercepts that represent the individually effective doses, e. g., ED50 values of each. This line is the reference for distinguishing additive from nonadditive interactions accordingly as the tested combination is on or off this line. Discussed here are the assumptions that underlie this linear plot. Specifically we show that a combination of drugs with a variable potency ratio, exemplified by a full and a partial agonist, lead to curvilinear isoboles of additivity that may erroneously be attributed to either synergism or subadditivity.