药物重要脏性及其早期预测方法的探讨.PDFVIP

- 8 - Drug Evaluation Research 第 34 卷 第 1 期 2011 年 2 月 药物重要脏器毒性及其早期预测方法的探讨 1 1 2, 3 2 孟凡翠 ，徐为人 ，张宗鹏 ，汤立达 1. 天津药物研究院 天津市新药设计与发现重点实验室，天津 300193 2. 天津药物研究院 天津药代与药效学省部共建重点实验室，天津 300193 3. 天津药物研究院 新药评价中心，天津 300193 摘 要：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。 关键词：药物毒性；代谢产物；离子通道；离子转运体；反应活性 中图分类号：R965.3 文献标志码：A 文章编号：1674 - 6376 (2011) 01 - 0008 -07 Drug toxicity upon important organs and prediction in early development 1 1 2, 3 2 MENG Fan-cui , XU Wei-ren , ZHANG Zong-peng , TANG Li-da 1. Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China; 2. Tianjin State Key Laboratory of Pharmacokinetics and Pharmacodynamics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China; 3. Drug Evaluation Center, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China Abstract: 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. Key words: drug toxicity; metabolite; ion