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Computational translation of drug effects from animal experiments to human ventricular myocytes.
- Source :
-
Scientific reports [Sci Rep] 2020 Jun 29; Vol. 10 (1), pp. 10537. Date of Electronic Publication: 2020 Jun 29. - Publication Year :
- 2020
-
Abstract
- Using animal cells and tissues as precise measuring devices for developing new drugs presents a long-standing challenge for the pharmaceutical industry. Despite the very significant resources that continue to be dedicated to animal testing of new compounds, only qualitative results can be obtained. This often results in both false positives and false negatives. Here, we show how the effect of drugs applied to animal ventricular myocytes can be translated, quantitatively, to estimate a number of different effects of the same drug on human cardiomyocytes. We illustrate and validate our methodology by translating, from animal to human, the effect of dofetilide applied to dog cardiomyocytes, the effect of E-4031 applied to zebrafish cardiomyocytes, and, finally, the effect of sotalol applied to rabbit cardiomyocytes. In all cases, the accuracy of our quantitative estimates are demonstrated. Our computations reveal that, in principle, electrophysiological data from testing using animal ventricular myocytes, can give precise, quantitative estimates of the effect of new compounds on human cardiomyocytes.
- Subjects :
- Action Potentials drug effects
Animals
Dogs
Heart Ventricles cytology
Humans
Models, Cardiovascular
Myocytes, Cardiac cytology
Rabbits
Translational Research, Biomedical
Anti-Arrhythmia Agents pharmacology
Heart Ventricles drug effects
Myocytes, Cardiac drug effects
Phenethylamines pharmacology
Sotalol pharmacology
Sulfonamides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 32601303
- Full Text :
- https://doi.org/10.1038/s41598-020-66910-0