The Use of Translational Modelling and Simulation to Develop Immunomodulatory Therapy as an Adjunct to Antibiotic Treatment in the Context of Pneumonia Article Swipe
Robin Michelet
,
Moreno Ursino
,
Sandrine Boulet
,
Sebastian Franck
,
Fiordiligie Casilag
,
Mara Baldry
,
Jens Rolff
,
Madelé van Dyk
,
Sebastian G. Wicha
,
Jean‐Claude Sirard
,
Emmanuelle Comets
,
Sarah Zohar
,
Charlotte Kloft
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3390/pharmaceutics13050601
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3390/pharmaceutics13050601
The treatment of respiratory tract infections is threatened by the emergence of bacterial resistance. Immunomodulatory drugs, which enhance airway innate immune defenses, may improve therapeutic outcome. In this concept paper, we aim to highlight the utility of pharmacometrics and Bayesian inference in the development of immunomodulatory therapeutic agents as an adjunct to antibiotics in the context of pneumonia. For this, two case studies of translational modelling and simulation frameworks are introduced for these types of drugs up to clinical use. First, we evaluate the pharmacokinetic/pharmacodynamic relationship of an experimental combination of amoxicillin and a TLR4 agonist, monophosphoryl lipid A, by developing a pharmacometric model accounting for interaction and potential translation to humans. Capitalizing on this knowledge and associating clinical trial extrapolation and statistical modelling approaches, we then investigate the TLR5 agonist flagellin. The resulting workflow combines expert and prior knowledge on the compound with the in vitro and in vivo data generated during exploratory studies in order to construct high-dimensional models considering the pharmacokinetics and pharmacodynamics of the compound. This workflow can be used to refine preclinical experiments, estimate the best doses for human studies, and create an adaptive knowledge-based design for the next phases of clinical development.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/pharmaceutics13050601
- https://www.mdpi.com/1999-4923/13/5/601/pdf?version=1619079057
- OA Status
- gold
- Cited By
- 4
- References
- 81
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3154524738
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3154524738Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3390/pharmaceutics13050601Digital Object Identifier
- Title
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The Use of Translational Modelling and Simulation to Develop Immunomodulatory Therapy as an Adjunct to Antibiotic Treatment in the Context of PneumoniaWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2021Year of publication
- Publication date
-
2021-04-22Full publication date if available
- Authors
-
Robin Michelet, Moreno Ursino, Sandrine Boulet, Sebastian Franck, Fiordiligie Casilag, Mara Baldry, Jens Rolff, Madelé van Dyk, Sebastian G. Wicha, Jean‐Claude Sirard, Emmanuelle Comets, Sarah Zohar, Charlotte KloftList of authors in order
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https://doi.org/10.3390/pharmaceutics13050601Publisher landing page
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https://www.mdpi.com/1999-4923/13/5/601/pdf?version=1619079057Direct link to full text PDF
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
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https://www.mdpi.com/1999-4923/13/5/601/pdf?version=1619079057Direct OA link when available
- Concepts
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Context (archaeology), Clinical trial, Medicine, Intensive care medicine, Computational biology, Computer science, Pharmacology, Biology, Internal medicine, PaleontologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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4Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2, 2024: 1, 2022: 1Per-year citation counts (last 5 years)
- References (count)
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81Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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