Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing.
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-chann...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2012
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| _version_ | 1826297922052947968 |
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| author | Mirams, G Davies, MR Cui, Y Kohl, P Noble, D |
| author_facet | Mirams, G Davies, MR Cui, Y Kohl, P Noble, D |
| author_sort | Mirams, G |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T04:39:00Z |
| format | Journal article |
| id | oxford-uuid:d0f69a6a-5765-4ade-a946-1695873608df |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:39:00Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:d0f69a6a-5765-4ade-a946-1695873608df2022-03-27T07:53:43ZApplication of cardiac electrophysiology simulations to pro-arrhythmic safety testing.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d0f69a6a-5765-4ade-a946-1695873608dfEnglishSymplectic Elements at Oxford2012Mirams, GDavies, MRCui, YKohl, PNoble, DConcerns 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. |
| spellingShingle | Mirams, G Davies, MR Cui, Y Kohl, P Noble, D Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing. |
| title | Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing. |
| title_full | Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing. |
| title_fullStr | Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing. |
| title_full_unstemmed | Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing. |
| title_short | Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing. |
| title_sort | application of cardiac electrophysiology simulations to pro arrhythmic safety testing |
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