Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing

作者：Mirams Gary R; Davies Mark R; Cui Yi; Kohl Peter^*; Noble Denis

来源：British Journal of Pharmacology, 2012, 167(5): 932-945.

DOI：10.1111/j.1476-5381.2012.02020.x

• arrhythmia
• Torsade de Pointes
• computer model
• hERG
• QT prolongation

Concerns over cardiac side effects are the largest single cause of compound attrition during pharmaceutical drug development. For a number of years, biophysically detailed mathematical models of cardiac electrical activity have been used to explore how a compound, interfering with specific ion-channel function, may explain effects at the cell-, tissue- and organ-scales. With the advent of high-throughput screening of multiple ion channels in the wet-lab, and improvements in computational modelling of their effects on cardiac cell activity, more reliable prediction of pro-arrhythmic risk is becoming possible at the earliest stages of drug development. In this paper, we review the current use of biophysically detailed mathematical models of cardiac myocyte electrical activity in drug safety testing, and suggest future directions to employ the full potential of this approach. LINKED ARTICLE This article is commented on by Gintant, pp. 929931 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2012.02096.x

• 出版日期2012-11