药物重要脏器毒性及其早期预测方法的探讨

Drug toxicity upon important organs and prediction in early development

毒性是导致药物研发失败的主要原因之一。为了避免在药物开发晚期发现毒性导致的昂贵代价,尽早确定药物潜在的毒性问题非常重要。通过对药物产生的肝脏、心脏和肾脏毒性的机制进行分析,并对现有的毒性预测方法进行综述,提出可以从代谢产物反应活性、离子转运体、离子通道等3方面综合分析药物产生毒性的可能性,从而提高重要脏器严重毒性预测的准确性。

Toxicity is one of the major reasons causing a drug failure.Therefore,in order to advoid and reduce the high price of drug failures due to the toxicity in late development,it is essential to determine potential toxicity problems as early as possible.In this paper the mechanism of drug-caused toxicity in various injured organs,such as liver,heart,and kedney,was analyzed and summarized and computational methods corresponding to different toxicity mechanisms have been listed to predict toxicity of drugs.These computational methods could be feasible in the comprehensive analysis on reactivity of metabolite,ion transporter,and ion channel,and may be useful in improving the accuracy of toxicity prediction.