Reverse Translation in PBPK and QSP: Going Backwards in Order to Go Forward With Confidence
Open accessAbstract
Significant events have taken place shaping the recent industrialization of physiologically based pharmacokinetic in vitro–in vivo extrapolation (PBPK‐IVIVE) use in drug development. Due to our knowledge gaps about drug‐independent systems parameters, there are limitations in the use of purely IVIVE‐based (bottom‐up) approaches. This has encouraged combining the classical data analysis (top‐down) with PBPK‐IVIVE‐linked models in order to optimize model parameters by taking advantage of observed clinical data. This concept, when initiated after clinical observations, can be viewed as “reverse translation,” since it refers back to available systems information preclinical data before trying to describe the observations. This review demonstrates the advantages of such strategies in filling knowledge gaps and discusses the perceived hurdles in widening applications. It is paramount that no clinical data are assessed on their own, but in conjunction with other studies for that drug in different populations and/or other similar drugs in the same population.
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Various terminology has been used to describe model credibility and V&V activities across MIDD approaches, including PBPK and quantitative systems pharmacology.
“Various terminology has been used to describe model credibility and V&V activities across MIDD approaches, including PBPK and quantitative systems pharmacology.20”
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References 22 · Cited by 90
Research works printed but not linked: 1
- [7]Doki, K., Darwich, A.S., Achour, B., Tornio, A., Backman, J.T. & Rostami‐Hodjegan, A. Accounting for inter‐correlation between hepatic CYP enzymes when predicting drug‐drug interactions and their inter‐individual variability. Br. J. Clin. Pharmacol. (Under Review).
- Authors
- Rostami‐Hodjegan, A.
- Affiliations
- University of Manchester (GB)
- Corresponding author
- Rostami‐Hodjegan, Amin
- Venue
- Clinical Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2017-11-09
- Volume
- 103
- Issue
- 2
- Pages
- 224-232
- ISSN
- 0009-9236 (ISSN-L)
- 1532-6535
- PMC
- PMC5813098
- OpenAlex
- W2762416511
- Cited by
- 90
- References
- 22
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 11 · 2023: 9 · 2022: 15 · 2021: 14 · 2020: 11 · 2019: 10 · 2018: 11
- FWCI
- 9.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical Pharmacology & Therapeutics (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, cc-by-nc)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Keywords
- reverse translation, physiologically based pharmacokinetic modeling, quantitative systems pharmacology, in vitro-in vivo extrapolation, model parameter optimization, clinical data integration, preclinical evidence, drug development
- MeSH terms
- Data Accuracy, Drug Development, Animals, Female, Humans, Kidney, Kidney Diseases, Liver, Male, Models, Theoretical, Pharmacokinetics, Pregnancy, Databases, Factual, Risk Assessment, Evidence-Based Medicine, Models, Animal, Systems Biology, Cytochrome P-450 CYP3A, Drug Discovery, Translational Research, Biomedical, Data Mining, Patient Safety, Renal Elimination
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