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In silico modeling and simulation of organ-on-a-chip systems to support data analysis and a priori experimental design.
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- معلومة اضافية
- المصدر:
Publisher: Wiley Country of Publication: United States NLM ID: 101580011 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2163-8306 (Electronic) Linking ISSN: 21638306 NLM ISO Abbreviation: CPT Pharmacometrics Syst Pharmacol Subsets: MEDLINE
- بيانات النشر:
Publication: 2015- : Hoboken, NJ : Wiley
Original Publication: New York, NY : Nature Pub. Group
- الموضوع:
- نبذة مختصرة :
Organ-on-a-chip (OoC) systems are a promising new class of in vitro devices that can combine various tissues, cultured in different compartments, linked by media flow. The properties of these novel in vitro systems linked to increased physiological relevance of culture conditions may lead to more in vivo-relevant cell phenotypes, enabling better in vitro pharmacology and toxicology assessment. Improved cell activities combined with longer lasting cultures offer opportunities to improve the characterization of absorption, distribution, metabolism, and excretion (ADME) processes, potentially leading to more accurate prediction of human pharmacokinetics (PKs). The inclusion of barrier tissue elements and metabolically competent tissue types results in complex concentration-time profiles (in vitro PK) for test drugs and their metabolites that require appropriate mathematical modeling of in vitro data for parameter estimation. In particular, modeling is critical to estimate in vitro ADME parameters when multiple different tissues are combined in a single device. Therefore, sophisticated in silico data analysis and a priori experimental design are highly recommended for OoC experiments in a manner not needed with standard ADME screening. The design of the experiment should be optimized based on an investigation of the structural characteristics of the in vitro system, the ADME features of the test compound and any available knowledge of cell phenotypes. This tutorial aims to provide such a modeling framework to inform experimental design and refine parameter estimation in a Gut-Liver OoC (the most studied multi-organ systems to predict the oral drug PKs) to improve translatability of data generated in such complex cellular systems.
(© 2024 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
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- الموضوع:
Date Created: 20240215 Date Completed: 20240415 Latest Revision: 20240522
- الموضوع:
20240522
- الرقم المعرف:
PMC11015085
- الرقم المعرف:
10.1002/psp4.13110
- الرقم المعرف:
38356302
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