Effects of the introduction of in vitro assays on the use of experimental animals in pharmacological research
Effects of the introduction of in vitro assays on the use of experimental animals in pharmacological research
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DOI：
10.1177/026119290703500211
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发表时间：
2007-05-01
影响因子：
2.7
通讯作者：
Hendriksen, Coenraad F. M.
中科院分区：
文献类型：
--
作者：
Verbost, Pieter M.;van der Vak, Jan;Hendriksen, Coenraad F. M.
药理学研究中体外测定的引入导致了实验动物数量的减少。但这种减少的程度是多少？什么时候真正开始减少的？本报告描述了一家中型制药公司发生的事件。对过去 12 年收集的数据的分析显示，合成每种化合物所用的实验动物数量减少了五倍。在“高通量筛选”中正在评估潜在生物活性的化合物库（随机合成分子的大量集合）中的化合物不包括在该分析中。多年来，实验中动物的（平均）不适程度变化不大；通常观察到的变化范围为 1.5 至 2.0（范围为 1-6）。 1997年，实验小鼠的不适评分达到了峰值，这可以通过关节炎模型的启动来解释，这些模型随后经过改进，导致痛苦程度降低。可以得出的结论是，体外测定的引入确实显着减少了选择良好化合物（即可以进入临床前毒理学阶段的化合物）所需的实验动物数量。然而，这种发展似乎已被临床研究中新化学实体的低存活率所抵消，导致每年实际进入市场的化合物数量减少。从“生产力的角度”来看，选择适销对路的药物所需的实验动物数量在过去十年中没有太大变化。
The introduction of in vitro assays in pharmacological research has led to a reduction in the number of experimental animals used. But what has been the degree of this reduction, and when did it really start? This report describes the events in a medium-sized pharmaceutical company. Analysis of data collected over the last 12 years shows a five-fold reduction in the number of experimental animals used per compound synthesised. Compounds from compound libraries (large collections of randomly-synthesised molecules) that are being assessed for potential bioactivity in 'high-throughput screening' were not included in this analysis. Over the years, the (average) degree of discomfort for the animals in the experiments did not vary much; with variation generally observed from 1.5 to 2.0 (on a scale from 1-6). There was a peak in the discomfort score of experimental mice in 1997, which could be explained by the initiation of arthritis models that were subsequently refined, resulting in a lower degree of suffering. It might be concluded that the introduction of in vitro assays has indeed brought about a significant reduction in the number of experimental animals required to select a good compound (i.e. one that could progress to the preclinical toxicology phase). However, this development appears to have been neutralised by the low survival rate of new chemical entities in clinical studies, leading to a lower number of compounds per annum that actually reach the market place. Put in this 'productivity perspective', the number of experimental animals required to select a marketable drug has not much changed in the last decade.