摘要
药物致心律失常风险是影响药物开发和使用的主要因素之一,在新药研发与评价中占据重要地位。自2005年起,国际上新药心律失常风险评价基本参照国际人用药品注册技术协调会(International Council on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use,ICH) S7B和E14指导原则进行,但是上述指导原则存在一定局限性。最新研究证据对浓度-QT分析价值的肯定和心律失常体外综合评价方法(Comprehensive in vitro Proarrhythmia Assay,Ci PA)项目的推进,带来了心律失常评价体系构建新的思考。本文对目前主要临床前和临床评价方法进行综述,并从成本、技术门槛、准确性和效率层面进行系统比较,探索建立适合中国研发现状的心脏毒性评价体系,科学地评价和监管药物致心律失常风险。
Assessment of drug-induced arrhythmia,which can affect drug development and usage,is one of the most significant parts of drug development and evaluation.Since 2005,proarrhythmia risk evaluation of new drugs has been conducted according to the International Council on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use(ICH)S7B and E14 guidelines.However,the guidelines are not specific for predicting which drugs are proarrhythmic.The affirmation of concentration-QT analysis and promoting of the comprehensive in vitro proarrhythmia assay(CiPA)paradigm give rise to our thinking for the system construction of proarrhythmia risk evaluation.This paper reviews and systematically compares the current preclinical and clinical approaches from the aspects of cost,technical threshold,accuracy and efficiency.On this basis,a cardiac toxicity assessment system for China may be developed for evaluating and monitoring the risk of proarrhythmia scientifically.
作者
曹青青
杨劲
CAO Qing-qing;YANG Jin(Center of Drug Metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing 210009,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2019年第18期2225-2231,共7页
Chinese Journal of New Drugs
