提高药物研发中心血管毒性的预测性研究进展

Advance of improvment of the prediction on cardiovascular toxicity in the drug development

心血管风险仍然是导致新药研发终止、发生严重不良反应甚至撤离市场的主要因素。虽然心肌离子通道检测、动作电位检测和遥测技术的运用大大提高了对药物诱导心律失常的预测的准确性,并且降低了安全风险,但对药物引起的其他心脏毒性如心肌收缩功能异常、心肌缺血、心肌损伤及心衰等仍缺乏有效的检测方法和技术,而目前在药物研发阶段对这些心血管安全风险没有像心律失常一样引起足够的关注。本文综述了近期的研究进展,全面阐述在药物研发阶段及临床应用中主要的心血管风险、如何检测这些风险以及现有安全评价手段的准确性和预测性和新方法新技术的研究与运用等。

Cardiovascular risk remains a major reason that causes drug attrition during preclinical and clinical development,adverse drug reactions,and withdrawal from market.These tests of cardiac ion channels screening,action potential recording,and ECG monitoring by telemeter have improved the prediction for cardiac arrhythmia and decreased cardiac risk.However,there are still no better methods to monitor other cardiac toxicities,such as cardiac contractility,myocardial ischemia,and heart failure.Moreover,we have not paid enough attention to these cardiac toxicities compared to arrhythmia during drug development.This paper reviews the recent research progress,and comprehensive exposition of what is in the stage of drug development and clinical application of major cardiovascular risk,how to detect these risks,the existing safety assessment methods of accuracy and predictability,research and application of new methods and new technology.