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Leveraging model-informed approaches for drug discovery and development in the cardiovascular space

Cardiovascular disease remains a significant global health burden, and development of cardiovascular drugs in the current regulatory environment often demands large and expensive cardiovascular outcome trials. Thus, the use of quantitative pharmacometric approaches which can help enable early Go/No...

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Autores principales: Dockendorf, Marissa F., Vargo, Ryan C., Gheyas, Ferdous, Chain, Anne S. Y., Chatterjee, Manash S., Wenning, Larissa A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5953982/
https://www.ncbi.nlm.nih.gov/pubmed/29353335
http://dx.doi.org/10.1007/s10928-018-9571-3
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author Dockendorf, Marissa F.
Vargo, Ryan C.
Gheyas, Ferdous
Chain, Anne S. Y.
Chatterjee, Manash S.
Wenning, Larissa A.
author_facet Dockendorf, Marissa F.
Vargo, Ryan C.
Gheyas, Ferdous
Chain, Anne S. Y.
Chatterjee, Manash S.
Wenning, Larissa A.
author_sort Dockendorf, Marissa F.
collection PubMed
description Cardiovascular disease remains a significant global health burden, and development of cardiovascular drugs in the current regulatory environment often demands large and expensive cardiovascular outcome trials. Thus, the use of quantitative pharmacometric approaches which can help enable early Go/No Go decision making, ensure appropriate dose selection, and increase the likelihood of successful clinical trials, have become increasingly important to help reduce the risk of failed cardiovascular outcomes studies. In addition, cardiovascular safety is an important consideration for many drug development programs, whether or not the drug is designed to treat cardiovascular disease; modeling and simulation approaches also have utility in assessing risk in this area. Herein, examples of modeling and simulation applied at various stages of drug development, spanning from the discovery stage through late-stage clinical development, for cardiovascular programs are presented. Examples of how modeling approaches have been utilized in early development programs across various therapeutic areas to help inform strategies to mitigate the risk of cardiovascular-related adverse events, such as QTc prolongation and changes in blood pressure, are also presented. These examples demonstrate how more informed drug development decisions can be enabled by modeling and simulation approaches in the cardiovascular area.
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spelling pubmed-59539822018-05-18 Leveraging model-informed approaches for drug discovery and development in the cardiovascular space Dockendorf, Marissa F. Vargo, Ryan C. Gheyas, Ferdous Chain, Anne S. Y. Chatterjee, Manash S. Wenning, Larissa A. J Pharmacokinet Pharmacodyn Review Paper Cardiovascular disease remains a significant global health burden, and development of cardiovascular drugs in the current regulatory environment often demands large and expensive cardiovascular outcome trials. Thus, the use of quantitative pharmacometric approaches which can help enable early Go/No Go decision making, ensure appropriate dose selection, and increase the likelihood of successful clinical trials, have become increasingly important to help reduce the risk of failed cardiovascular outcomes studies. In addition, cardiovascular safety is an important consideration for many drug development programs, whether or not the drug is designed to treat cardiovascular disease; modeling and simulation approaches also have utility in assessing risk in this area. Herein, examples of modeling and simulation applied at various stages of drug development, spanning from the discovery stage through late-stage clinical development, for cardiovascular programs are presented. Examples of how modeling approaches have been utilized in early development programs across various therapeutic areas to help inform strategies to mitigate the risk of cardiovascular-related adverse events, such as QTc prolongation and changes in blood pressure, are also presented. These examples demonstrate how more informed drug development decisions can be enabled by modeling and simulation approaches in the cardiovascular area. Springer US 2018-01-20 2018 /pmc/articles/PMC5953982/ /pubmed/29353335 http://dx.doi.org/10.1007/s10928-018-9571-3 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Review Paper
Dockendorf, Marissa F.
Vargo, Ryan C.
Gheyas, Ferdous
Chain, Anne S. Y.
Chatterjee, Manash S.
Wenning, Larissa A.
Leveraging model-informed approaches for drug discovery and development in the cardiovascular space
title Leveraging model-informed approaches for drug discovery and development in the cardiovascular space
title_full Leveraging model-informed approaches for drug discovery and development in the cardiovascular space
title_fullStr Leveraging model-informed approaches for drug discovery and development in the cardiovascular space
title_full_unstemmed Leveraging model-informed approaches for drug discovery and development in the cardiovascular space
title_short Leveraging model-informed approaches for drug discovery and development in the cardiovascular space
title_sort leveraging model-informed approaches for drug discovery and development in the cardiovascular space
topic Review Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5953982/
https://www.ncbi.nlm.nih.gov/pubmed/29353335
http://dx.doi.org/10.1007/s10928-018-9571-3
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