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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Autor principal:	Lars Kuepfer
Formato:	article
Lenguaje:	EN
Publicado:	South Valley University 2019
Materias:	cross-species extrapolation inter-species extrapolation pbpk modelling pharmacology toxicology Agriculture S Veterinary medicine SF600-1100
Acceso en línea:	https://doaj.org/article/a94188f39ce3415882c79a550fba59d8
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spelling	oai:doaj.org-article:a94188f39ce3415882c79a550fba59d82021-12-02T08:51:46ZProspects and limitations of physiologically-based pharmacokinetic modelling for cross-species extrapolation10.21608/SVU.2019.14193.10202535-18262535-1877https://doaj.org/article/a94188f39ce3415882c79a550fba59d82019-07-01T00:00:00Zhttps://svu.journals.ekb.eg/article_38878.htmlhttps://doaj.org/toc/2535-1826https://doaj.org/toc/2535-1877The 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.Lars KuepferSouth Valley Universityarticlecross-species extrapolationinter-species extrapolationpbpk modellingpharmacologytoxicologyAgricultureSVeterinary medicineSF600-1100ENSVU-International Journal of Veterinary Sciences, Vol 2, Iss 2, Pp 45-51 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	cross-species extrapolation inter-species extrapolation pbpk modelling pharmacology toxicology Agriculture S Veterinary medicine SF600-1100
spellingShingle	cross-species extrapolation inter-species extrapolation pbpk modelling pharmacology toxicology Agriculture S Veterinary medicine SF600-1100 Lars Kuepfer Prospects and limitations of physiologically-based pharmacokinetic modelling for cross-species extrapolation
description	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.
format	article
author	Lars Kuepfer
author_facet	Lars Kuepfer
author_sort	Lars Kuepfer
title	Prospects and limitations of physiologically-based pharmacokinetic modelling for cross-species extrapolation
title_short	Prospects and limitations of physiologically-based pharmacokinetic modelling for cross-species extrapolation
title_full	Prospects and limitations of physiologically-based pharmacokinetic modelling for cross-species extrapolation
title_fullStr	Prospects and limitations of physiologically-based pharmacokinetic modelling for cross-species extrapolation
title_full_unstemmed	Prospects and limitations of physiologically-based pharmacokinetic modelling for cross-species extrapolation
title_sort	prospects and limitations of physiologically-based pharmacokinetic modelling for cross-species extrapolation
publisher	South Valley University
publishDate	2019
url	https://doaj.org/article/a94188f39ce3415882c79a550fba59d8
work_keys_str_mv	AT larskuepfer prospectsandlimitationsofphysiologicallybasedpharmacokineticmodellingforcrossspeciesextrapolation
_version_	1718398382226014208

Prospects and limitations of physiologically-based pharmacokinetic modelling for cross-species extrapolation

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