Challenges and opportunities with modelling and simulation in drug discovery and drug development
Abstract
The benefits of modelling and simulation at the pre-clinical stage of drug development can be realized through formal and realistic integration of data on physicochemical properties, pharmacokinetics, pharmacodynamics, formulation and safety. Such data integration and the powerful combination of physiologically based pharmacokinetic (PBPK) with pharmacokinetic-pharmacodynamic relationship (PK/PD) models provides the basis for quantitative outputs allowing comparisons across compounds and resulting in improved decision-making during the selection process. Such PBPK/PD evaluations provide crucial information on the potency and safety of drug candidates in vivo and the bridging of the PK/PD concept established during the pre-clinical phase to clinical studies. Modelling and simulation is required to address a number of key questions at the various stages of the drug-discovery and -development process. Such questions include the following. (1) What is the expected human PK profile for potential clinical candidate(s)? (2) Is this profile and its associated PD adequate for the given indication? (3) What is the optimal dosing schedule with respect to safety and efficacy? (4) Is a food effect expected? (5) How can formulation be improved and what is the potential benefit? (6) What is the expected variability and uncertainty in the predictions?
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- Authors
- Lavé, T., Parrott, N., Grimm, H. P., Fleury, A., & Reddy, M.
- Affiliations
- F. Hoffmann-La Roche AG (CH)
- Roche (United States) (US)
- Venue
- Xenobiotica
- Publisher
- Informa UK Limited
- Published
- 2007-11
- Volume
- 37
- Issue
- 10-11
- Pages
- 1295-1310
- ISSN
- 0049-8254 (ISSN-L)
- 1366-5928
- OpenAlex
- W1994206407
- Cited by
- 115
- References
- 47
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 8 · 2023: 5 · 2022: 9 · 2021: 2 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 1 · 2016: 5 · 2015: 2 · 2014: 11 · 2013: 6 · 2012: 9
- FWCI
- 9.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Xenobiotica (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- modeling and simulation, drug discovery, drug development, physiologically based pharmacokinetic modeling, pharmacokinetic-pharmacodynamic modeling, dosing schedule optimization, food effect, drug formulation, interindividual variability, forecast uncertainty, drug candidate selection
- MeSH terms
- Absorption, Animals, Biological Transport, Active, Drug Interactions, Food, Humans, Models, Biological, Drug Design, Xenobiotics
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