Biophysically detailed mathematical models of cardiac myocyte electrical activity combined with high-throughput screening enable more reliable prediction of pro-arrhythmic risk in early drug development.
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.
Mirams et al. (Wed,) conducted a review in Pro-arrhythmic risk in drug development. Biophysically detailed mathematical models of cardiac myocyte electrical activity was evaluated. Biophysically detailed mathematical models of cardiac myocyte electrical activity combined with high-throughput screening enable more reliable prediction of pro-arrhythmic risk in early drug development.