Halle W, Göres E, Baeger I
Institut für Pharmakologische Forschung, VEB im Pharmazeutischen Kombinat GERMED Dresden.
Pharmazie. 1987 Dec;42(12):848-50.
In this article we use the linear regression model to compare the values of IC50 and LD50 p.o. (mice and rats) taken from the literature and estimated in our laboratory. By this analysis it was found that for different substance classes a similar relationship exists between IC50 and LD50, even if different cell types or cellular activities were used for estimating the IC50 on the one hand and different modes of substance application in animal toxicity tests on the other hand. The minimum and maximum values of the measured LD50 (LD50G) registered in animal experiments deviated from the theoretical LD50 values (LD50T) on the (log transformed) regression line in approximately 77 per cent of the cases by the factor FG less than or equal to log 5 only. The linear correlation between IC50 and LD50 is to be expected only for such substances which do not act specifically via higher levels of integration, cell type specific reactions or metabolites, respectively. These and previously reported results indicate a certain general validity not only for the positive linear correlation between IC50 and LD50 but also for the predicting the LD50 in a relatively narrow dosage range on the basis of in vitro estimated IC50 values. With these results new possibilities were opened for reducing animal experiments to estimate LD50.
在本文中,我们使用线性回归模型来比较从文献中获取并在我们实验室中估算的口服IC50和LD50值(小鼠和大鼠)。通过该分析发现,对于不同的物质类别,IC50和LD50之间存在相似的关系,即使一方面用于估算IC50的细胞类型或细胞活性不同,另一方面动物毒性试验中的物质应用方式也不同。在动物实验中记录的实测LD50(LD50G)的最小值和最大值与(对数转换后的)回归线上的理论LD50值(LD50T)的偏差,在大约77%的情况下,仅因因子FG小于或等于log 5。IC50和LD50之间的线性相关性仅在那些不分别通过更高层次的整合、细胞类型特异性反应或代谢产物起作用的物质中才有望出现。这些结果以及先前报道的结果表明,不仅IC50和LD50之间的正线性相关性具有一定的普遍有效性,而且基于体外估算的IC50值在相对较窄的剂量范围内预测LD50也具有一定的普遍有效性。有了这些结果,为减少用于估算LD50的动物实验开辟了新的可能性。