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对QT间期延长的评估是小分子药物研发过程中的关键一步。ICHS7A/S7B为指导这个心血管风险评估提供了主要框架。ICH指南描述了通过体外hERG抑制、离体动作电位时间和在体心电图等三步法来评估QT间期延长。狗、猴、猪、兔、雪貂和豚鼠是常用实验动物用于体内的电生理研究,尤其使用清醒的比格犬。在这些指南中标准研究的基础上,大量新的非在体研发方法也在使用。例如受体结合对hERG抑制、离体兔子心脏或豚鼠心脏灌流等方法。这些模型和临床都有较好的相关性,并且具有成本低廉、实验周期短的特点。因此能够帮助快速准确的预测潜在的心脏病风险,从而加速小分子研发的进程。
The assessment of QT prolongation is a crucial step in the development of small molecule drugs. ICHS7A / S7B provides the main framework for guiding this cardiovascular risk assessment. The ICH guidelines describe the assessment of QT prolongation by a three-step, in vitro hERG inhibition, ex vivo action potential time, and in-vivo electrocardiogram. Dogs, monkeys, pigs, rabbits, ferrets, and guinea pigs are commonly used experimental animals for in vivo electrophysiological studies, especially with conscious Beagle dogs. Based on the standard studies in these guidelines, a number of new non-in-vivo R & D methods are also in use. For example, hERG inhibition of receptor binding, isolated rabbit heart or guinea pig cardiac perfusion and other methods. These models have a good correlation with clinical, and have the characteristics of low cost and short experimental period. So it can help predict the potential risk of heart disease quickly and accurately, thus accelerating the development of small molecules.