The virtue of translational PKPD modeling in drug discovery: selecting the right clinical candidate while sparing animal lives
Abstract
Translational pharmacokinetic-pharmacodynamic (PKPD) modeling has been fully implemented at AstraZeneca's drug discovery unit for central nervous system and pain indications to facilitate timely progression of the right compound to clinical studies, simultaneously assuring essential preclinical efficacy and safety knowledge. This review illustrates the impact of a translational PKPD paradigm with examples from drug discovery programs. Paradoxically, laboratory animal use decreased owing to better understanding of in vitro-in vivo relationships, optimized in vivo study designs, meta-analyses and hypothesis testing using simulations. From an ethical and effectivity perspective, we advocate that translational PKPD approaches should be implemented more broadly in drug discovery.
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Societal impact of modeling includes enhanced 3Rs of animal usage, reduced patient burden, and development of scientific talent.
“Finally, there is the societal impact, including the enhanced 3Rs of animal usage,83 reduced patient burden, or development of scientific talent among others.”
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- Authors
- Bueters, T., Ploeger, B. A., & Visser, S. A. G.
- Affiliations
- AstraZeneca (Sweden) (SE)
- Corresponding author
- Bueters, Tjerk
- Venue
- Drug Discovery Today
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 18
- Issue
- 17-18
- Pages
- 853-862
- ISSN
- 1359-6446 (ISSN-L)
- OpenAlex
- W1990797762
- Cited by
- 43
- References
- 1
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 1 · 2020: 5 · 2019: 3 · 2018: 1 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 4 · 2013: 4
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Discovery Today (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AstraZeneca
- Topics
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Keywords
- pharmacokinetics/pharmacodynamics, drug discovery, central nervous system drugs, animal use reduction, in vitro-in vivo extrapolation, preclinical study design, meta-analysis, animal welfare
- MeSH terms
- Animals, Animal Testing Alternatives, Dose-Response Relationship, Drug, Pharmaceutical Preparations, Humans, Models, Biological, Pharmacokinetics, Species Specificity, Structure-Activity Relationship, Toxicology, Molecular Structure, Risk Assessment, Drug Discovery, Translational Research, Biomedical, Molecular Targeted Therapy, Patient Safety
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