Prospects and limitations of physiologically-based pharmacokinetic modelling for cross-species extrapolation
The transition from experimental findings in animal models to clinical applications in human patients is a key challenge in pharmacology and toxicology. To date, this step still inhibits a significant level of uncertainty explaining amongst others the continuously high attrition rates in pharmace...
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
South Valley University
2019
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/a94188f39ce3415882c79a550fba59d8 |
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| Sumario: | The transition from experimental findings in animal models to clinical applications in human
patients is a key challenge in pharmacology and toxicology. To date, this step still inhibits a
significant level of uncertainty explaining amongst others the continuously high attrition rates in
pharmaceutical development programs. Computational modelling bears the promise to support
cross-species extrapolation through mechanistic descriptions of relevant physiological processes.
In this review, the benefits and limitations of computational approaches for clinical translation
are discussed and the needs for future applications are outlined. A particular focus is laid on the
differentiation between pharmacokinetics and pharmacodynamics. While the former determines
drug exposure in plasma or specific tissues, the latter describes the resulting response, i.e. the
therapeutic outcome or an adverse event. Based on a previous study it is argued that the main
challenges for cross-species extrapolation is genetic divergence between different animal models
and humans which will require novel inter-disciplinary concepts for clinical translation in the
future. |
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