Current approaches to assess QTc prolongation for small molecule drug development
10.3867/j.issn.1000-3002.2012.02.001
- VernacularTitle:当前对小分子药物致QTc间期延长评价的探索
- Author:
H.chen VICTOR
;
Shuilin XIE
;
Renke DAI
- Publication Type:Journal Article
- Keywords:
QT interval prolongation;
ECG;
hERG;
Cardiotoxicity;
Nonclinical safety evaluation
- From:
Chinese Journal of Pharmacology and Toxicology
2012;26(2):127-130
- CountryChina
- Language:Chinese
-
Abstract:
Assessment of QTc prolongation is a critical step for small molecule drug development.ICH S7B continues to be the main frame to guide the assessment for this potential cardiovascular risk.The ICH guideline outlines a 3-step approach to QTc prolongation,including in vitro bERG inhibition,ex vivo action potential duration (APD),and in vivo animal telemetry approch.Dog,monkey,swine,rabbit,ferret,and guinea pig are the common laboratory animals used for in vivo electrophysiology studies,especially using conscious Beagle Dog. In addition to all these guideline standard studies,many newly developed approaches,such as receptor binding for hERG inhibition,ex vivo methods such as perfused rabbit heart or guinea pig heartare are useful models for this purpose.All these methods display good correlation to clinic outcomes,and are low cost and have rapid turn-around time in nature; so that,they can help rapidly and predict this potential cardiac liability,resulting into accelerating process for small molecule drug candidate development.
