Gennings C, Carter W H, Campbell E D, Staniswalis J G, Martin T J, Martin B R, White K L
Department of Biostatics, Medical College of Virginia/Virginia Commonwealth University, Richmond.
J Pharmacol Exp Ther. 1990 Jan;252(1):208-17.
Isobolograms have been widely used to characterize the nature of the interaction between combinations of drugs or chemicals. Some authors have applied this technique without accounting for the variability in the data or without adjusting for multiple comparisons to the line of additivity. This paper develops a graphical procedure which takes into account the variability of the data and which maintains favorable statistical properties. The isobolographic procedure utilized is illustrated by using three classical pharmacological drug combinations in female ICR mice. An additive relationship is illustrated with the loss of righting reflex after combinations of doses of sodium hexobarbital with itself. An antagonistic relationship is illustrated with the protection by mecamylamine of nicotine-induced lethality. A synergistic relationship is illustrated with the loss of righting reflex after combinations of ethanol and chloral hydrate. The procedure's statistical properties (level of significance and power) were determined using a simulation study. The isobolographic procedures developed here are applicable for quantal, continuous and count data. These procedures are applicable for identifying beneficial drug combinations, or conversely, identifying hazards resulting from exposure to multiple toxicants.
等效线图已被广泛用于表征药物或化学物质组合之间相互作用的性质。一些作者应用了该技术，但没有考虑数据的变异性，也没有针对与相加线的多重比较进行调整。本文开发了一种图形程序，该程序考虑了数据的变异性，并保持了良好的统计特性。通过在雌性ICR小鼠中使用三种经典的药理药物组合来说明所采用的等效线图程序。用己巴比妥钠剂量组合后翻正反射的丧失来说明相加关系。用美加明对尼古丁诱导的致死性的保护作用来说明拮抗关系。用乙醇和水合氯醛组合后翻正反射的丧失来说明协同关系。使用模拟研究确定了该程序的统计特性（显著性水平和检验效能）。这里开发的等效线图程序适用于定量、连续和计数数据。这些程序适用于识别有益的药物组合，或者相反，识别接触多种毒物所产生的危害。
