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Computational translation of drug effects from animal experiments to human ventricular myocytes.

Authors :
Tveito A
Jæger KH
Maleckar MM
Giles WR
Wall S
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.

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