药物QT间期延长潜在作用非临床研究技术指导原则(国家食药监总局通告2014年第4号) .. ...

2023-3-7 12:35| 发布者: 启疾光| 查看: 810| 评论: 0|来自: 国家药监局

摘要: 本指则适用于中药、天然药物和化学药物。主要是关于评价受试物延迟心室复极化潜在作用的非临床研究策略,以及对非临床研究信息的分析和综合风险性评估。QT间期研究结果可以和其他信息一起,用来阐明药物作用机制,以 ...


心肌动作电位试验中的重要参数项目

三浓度检测参数项目

测试

测试浓度数                 

3

检测每一个受试物所需的蒲肯野纤维数或心肌细胞数

4

用于对照品的蒲肯野纤维数或心肌细胞数

4

累积曲线

+

在生理温度 (37º±1º C) 下进行试验

+

统计学分析

+

如果系GLP实验室,收集样本的分析

+

报告

+

如果是GLP实验室,要求有质量保证部门(Quality Assurence Unit, QAU)的检查,包括同步、数据和报告的检查

+

 

可参考的文献

1.  De Clerck F et al, In vivo measurement of QT prolongation, dispersion and arrhythmogenesis: application to the preclinical cardiovascular safety pharmacology of a new chemical entity, FundamClinPharmacol, 2002;16:125-40.

2.  Sanguinetti MC, Mitcheson JS, Predicting drug-hERG channel interactions that cause acquired long QT syndrome, Trends Pharmacol Sci,2005;26: 119-24.  

3.  Lawrence CL et al, Nonclinical proarrhythmia models: Predicting Torsades de Pointes, J PharmacolToxicol Methods,2005; 52: 46–59

4.  Guth BD, Preclinical cardiovascular risk assessment in modern drug development, ToxicolSci, 2007; 97, 4–20.  

5.  KettenhofenR,Bohlen H, Preclinical assessment of cardiac toxicity,   Drug Discov Today, 2008;13:702-7.  

6.  Sugiyama A Sensitive and reliable proarrhythmia in vivo animal models for predicting drug-induced torsades depointes in patients with remodelled hearts, Br J Pharmacol, 2008;154:1528-37.  

7.  Valentin JP, Hammond T Safety and secondary pharmacology: Successes, threats, challenges and opportunities, JpharmacolToxicol Methods,2008;58: 77–87.

8.  Valentin JP etal A framework to assess the translation of safety pharmacology data to humans, J PharmacolToxicolMethods,2009;60:152–58

9.  Amanfu,RK , Saucerman, JJ, Cardiac models in drug discovery and development: a review, Crit Rev Biomed Eng,2011;39:379-95.

   10. Mikhailov D, Traebert M, Lü Q, Whitebread S, Egan W Should cardiosafety be ruled by hERG inhibition? Early testing scenarios and integrated risk assessment, (Bernard Faller and Laszlo Urban ed, Hit and Lead Profiling- Identification and Optimization of Drug-like Molecules, 2010; Wiley-VCH Verlag GmbH & Co KgaA.
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