Tallarida R J, Porreca F, Cowan A
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140.
Life Sci. 1989;45(11):947-61. doi: 10.1016/0024-3205(89)90148-3.
The use of more than one drug to achieve a desired effect has been a common practice in pharmacologic testing and in clinical practice. For example, combinations of analgesics are frequently prescribed with a view to enhancing pain relief and reducing adverse effects. It is also well established that administration of more than one drug may give effects that are greater than, or less than, the additive effect of each drug given individually. A non-mechanistic method of characterizing the effect resulting from the administration of two compounds is the isobologram. It is relatively simple to draw and interpret isobolograms. However, this graphical technique, which employs equieffective concentrations of individual drugs and combinations of these, obtains the concentrations as random variables from concentration-effect data, usually transformed to a parallel line assay. Thus, statistical confidence limits from such assays, as well as from non-parallel designs, must be expressed on the isobologram if this diagram is to establish superadditive, subadditive, or merely additive effects. We now present a detailed statistical analysis of the isobolographic method illustrated with examples of the statistical procedures, a rational basis for selecting proportions of each drug in the combination, and a relatively novel application of the isobolographic concept, i.e., interactions involving different anatomical sites.
使用多种药物以达到预期效果在药理学测试和临床实践中一直是常见做法。例如，经常开具镇痛药组合处方，目的是增强止痛效果并减少不良反应。还已充分证实，使用多种药物可能产生的效果大于或小于每种单独给药药物的相加效应。描述两种化合物给药后效果的一种非机械方法是等效线图。绘制和解释等效线图相对简单。然而，这种图形技术采用单个药物及其组合的等效浓度，从浓度-效应数据中获取浓度作为随机变量，通常转换为平行线测定法。因此，如果要通过该图确定超相加、次相加或仅相加效应，则必须在等效线图上表示此类测定以及非平行设计的统计置信限。我们现在通过统计程序示例对等效线图法进行详细的统计分析，给出选择组合中每种药物比例的合理依据，以及等效线图概念的一个相对新颖的应用，即涉及不同解剖部位的相互作用。
