| Title |
Top-down, Bottom-up and Middle-out Strategies for Drug Cardiac Safety Assessment via Modeling and Simulations
|
|---|---|
| Published in |
Current Pharmacology Reports, April 2016
|
| DOI | 10.1007/s40495-016-0060-3 |
| Pubmed ID | |
| Authors |
Zofia Tylutki, Sebastian Polak, Barbara Wiśniowska |
| Abstract |
Cardiac safety is an issue causing early terminations at various stages of drug development. Efforts are put into the elimination of false negatives as well as false positives resulting from the current testing paradigm. In silico approaches offer mathematical system and data description from the ion current, through cardiomyocytes level, up to incorporation of inter-individual variability at the population level. The article aims to review three main modelling and simulation approaches, i.e. "top-down" which refers to models built on the observed data, "bottom-up", which stands for a mechanistic description of human physiology, and "middle-out" which combines both strategies. Modelling and simulation is a well-established tool in the assessment of drug proarrhythmic potency with an impact on research and development as well as on regulatory decisions, and it is certainly here to stay. What is more, the shift to systems biology and physiology-based models makes the cardiac effect more predictable. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 49 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| India | 1 | 2% |
| Unknown | 48 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 11 | 22% |
| Student > Master | 8 | 16% |
| Researcher | 3 | 6% |
| Student > Bachelor | 2 | 4% |
| Student > Doctoral Student | 1 | 2% |
| Other | 4 | 8% |
| Unknown | 20 | 41% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 15 | 31% |
| Medicine and Dentistry | 6 | 12% |
| Engineering | 3 | 6% |
| Computer Science | 1 | 2% |
| Chemical Engineering | 1 | 2% |
| Other | 2 | 4% |
| Unknown | 21 | 43% |
Attention Score in Context
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