Cargando…

Quantitative Systems Pharmacology Models for a New International Cardiac Safety Regulatory Paradigm: An Overview of the Comprehensive In Vitro Proarrhythmia Assay In Silico Modeling Approach

As a relatively new discipline, quantitative systems pharmacology has seen a significant increase in the application and utility of drug development. One area that could greatly benefit from such an approach is in the proarrhythmia assessment of new drugs. The Comprehensive In Vitro Proarrhythmia As...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Zhihua, Garnett, Christine, Strauss, David G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617836/
https://www.ncbi.nlm.nih.gov/pubmed/31044559
http://dx.doi.org/10.1002/psp4.12423
_version_ 1783433782201679872
author Li, Zhihua
Garnett, Christine
Strauss, David G.
author_facet Li, Zhihua
Garnett, Christine
Strauss, David G.
author_sort Li, Zhihua
collection PubMed
description As a relatively new discipline, quantitative systems pharmacology has seen a significant increase in the application and utility of drug development. One area that could greatly benefit from such an approach is in the proarrhythmia assessment of new drugs. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) Initiative is a global public–private partnership project that has developed an integrated approach using mechanistic in silico models for proarrhythmia risk prediction. Progress to date has led to the formation of the International Council on Harmonisation Implementation Working Group to revise regulatory guidelines via the Questions‐and‐Answers process to address the best practices for proarrhythmia models and how they can impact clinical drug development. This article reviews the CiPA in silico model‐development process, focusing on its unique development and validation strategy, and summarizes the lessons learned as consideration points for the ongoing implementation of CiPA‐like in silico models in drug development.
format Online
Article
Text
id pubmed-6617836
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-66178362019-07-16 Quantitative Systems Pharmacology Models for a New International Cardiac Safety Regulatory Paradigm: An Overview of the Comprehensive In Vitro Proarrhythmia Assay In Silico Modeling Approach Li, Zhihua Garnett, Christine Strauss, David G. CPT Pharmacometrics Syst Pharmacol Reviews As a relatively new discipline, quantitative systems pharmacology has seen a significant increase in the application and utility of drug development. One area that could greatly benefit from such an approach is in the proarrhythmia assessment of new drugs. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) Initiative is a global public–private partnership project that has developed an integrated approach using mechanistic in silico models for proarrhythmia risk prediction. Progress to date has led to the formation of the International Council on Harmonisation Implementation Working Group to revise regulatory guidelines via the Questions‐and‐Answers process to address the best practices for proarrhythmia models and how they can impact clinical drug development. This article reviews the CiPA in silico model‐development process, focusing on its unique development and validation strategy, and summarizes the lessons learned as consideration points for the ongoing implementation of CiPA‐like in silico models in drug development. John Wiley and Sons Inc. 2019-06-17 2019-06 /pmc/articles/PMC6617836/ /pubmed/31044559 http://dx.doi.org/10.1002/psp4.12423 Text en Published 2019. This article is a U.S. Government work and is in the public domain in the USA. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Reviews
Li, Zhihua
Garnett, Christine
Strauss, David G.
Quantitative Systems Pharmacology Models for a New International Cardiac Safety Regulatory Paradigm: An Overview of the Comprehensive In Vitro Proarrhythmia Assay In Silico Modeling Approach
title Quantitative Systems Pharmacology Models for a New International Cardiac Safety Regulatory Paradigm: An Overview of the Comprehensive In Vitro Proarrhythmia Assay In Silico Modeling Approach
title_full Quantitative Systems Pharmacology Models for a New International Cardiac Safety Regulatory Paradigm: An Overview of the Comprehensive In Vitro Proarrhythmia Assay In Silico Modeling Approach
title_fullStr Quantitative Systems Pharmacology Models for a New International Cardiac Safety Regulatory Paradigm: An Overview of the Comprehensive In Vitro Proarrhythmia Assay In Silico Modeling Approach
title_full_unstemmed Quantitative Systems Pharmacology Models for a New International Cardiac Safety Regulatory Paradigm: An Overview of the Comprehensive In Vitro Proarrhythmia Assay In Silico Modeling Approach
title_short Quantitative Systems Pharmacology Models for a New International Cardiac Safety Regulatory Paradigm: An Overview of the Comprehensive In Vitro Proarrhythmia Assay In Silico Modeling Approach
title_sort quantitative systems pharmacology models for a new international cardiac safety regulatory paradigm: an overview of the comprehensive in vitro proarrhythmia assay in silico modeling approach
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617836/
https://www.ncbi.nlm.nih.gov/pubmed/31044559
http://dx.doi.org/10.1002/psp4.12423
work_keys_str_mv AT lizhihua quantitativesystemspharmacologymodelsforanewinternationalcardiacsafetyregulatoryparadigmanoverviewofthecomprehensiveinvitroproarrhythmiaassayinsilicomodelingapproach
AT garnettchristine quantitativesystemspharmacologymodelsforanewinternationalcardiacsafetyregulatoryparadigmanoverviewofthecomprehensiveinvitroproarrhythmiaassayinsilicomodelingapproach
AT straussdavidg quantitativesystemspharmacologymodelsforanewinternationalcardiacsafetyregulatoryparadigmanoverviewofthecomprehensiveinvitroproarrhythmiaassayinsilicomodelingapproach