Recent developments in using mechanistic cardiac modelling for drug safety evaluation

Drug Discov Today. 2016 Jun;21(6):924-38. doi: 10.1016/j.drudis.2016.02.003. Epub 2016 Feb 15.

Abstract

On the tenth anniversary of two key International Conference on Harmonisation (ICH) guidelines relating to cardiac proarrhythmic safety, an initiative aims to consider the implementation of a new paradigm that combines in vitro and in silico technologies to improve risk assessment. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative (co-sponsored by the Cardiac Safety Research Consortium, Health and Environmental Sciences Institute, Safety Pharmacology Society and FDA) is a bold and welcome step in using computational tools for regulatory decision making. This review compares and contrasts the state-of-the-art tools from empirical to mechanistic models of cardiac electrophysiology, and how they can and should be used in combination with experimental tests for compound decision making.

Publication types

  • Review

MeSH terms

  • Animals
  • Computer Simulation
  • Decision Making
  • Drug Discovery*
  • Heart / physiology*
  • Humans
  • Models, Biological*
  • Pharmacokinetics
  • Risk Assessment