In silico modeling and simulation of organ-on-a-chip systems to support data analysis and a priori experimental design.

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

Publication: 2015- : Hoboken, NJ : Wiley
Original Publication: New York, NY : Nature Pub. Group

Microphysiological Systems* ; Research Design*; Humans ; Liver/metabolism ; Computer Simulation

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.)

Biopharm Drug Dispos. 2017 Apr;38(3):187-208. (PMID: 28207929)
Drug Metab Dispos. 2010 Jul;38(7):1147-58. (PMID: 20368326)
Clin Pharmacol Ther. 2012 Jul;92(1):50-61. (PMID: 22644330)
Drug Metab Dispos. 2023 Dec 1;:. (PMID: 38050097)
Biopharm Drug Dispos. 2017 Mar;38(2):155-160. (PMID: 28039878)
Mol Pharm. 2023 Mar 6;20(3):1737-1749. (PMID: 36791335)
Sci Rep. 2015 Dec 04;5:17671. (PMID: 26635233)
Lab Chip. 2020 Feb 7;20(3):446-467. (PMID: 31932816)
Expert Opin Drug Metab Toxicol. 2021 Aug;17(8):969-986. (PMID: 33764248)
Drug Metab Dispos. 2021 Jun 1;:. (PMID: 34074732)
Clin Pharmacol Ther. 2013 Jul;94(1):64-79. (PMID: 23588311)
Br J Clin Pharmacol. 2003 Oct;56(4):433-40. (PMID: 12968989)
Pharm Stat. 2009 Jul-Sep;8(3):239-52. (PMID: 19009585)
ALTEX. 2022 Nov 03;40(3):408-424. (PMID: 36343109)
J Pharm Sci. 2016 Feb;105(2):915-924. (PMID: 26869436)
Comput Biol Med. 2010 Apr;40(4):402-7. (PMID: 20185123)
Paediatr Anaesth. 2015 Mar;25(3):222-30. (PMID: 25580772)
Mol Pharm. 2019 Nov 4;16(11):4551-4562. (PMID: 31525064)
Commun Biol. 2023 Mar 23;6(1):310. (PMID: 36959276)
Comput Methods Programs Biomed. 2007 Oct;88(1):52-61. (PMID: 17707944)
Drug Metab Dispos. 2020 Oct;48(10):861-872. (PMID: 32759366)
Pharmaceutics. 2022 Dec 24;15(1):. (PMID: 36678684)
Drug Metab Dispos. 2021 Sep;49(9):760-769. (PMID: 34187837)
Methods Mol Biol. 2005;290:207-29. (PMID: 15361665)
AAPS J. 2022 Mar 11;24(2):41. (PMID: 35277751)
Lab Chip. 2020 Feb 7;20(3):537-547. (PMID: 31930237)
J Pharmacol Exp Ther. 2015 Feb;352(2):358-67. (PMID: 25503386)
Lab Chip. 2022 Mar 15;22(6):1187-1205. (PMID: 35107462)
Pharmacol Rev. 2022 Jan;74(1):141-206. (PMID: 35017176)
Methods Mol Biol. 2014;1113:255-88. (PMID: 24523117)
Biomed Microdevices. 2017 Nov 7;19(4):100. (PMID: 29116458)
Curr Drug Metab. 2008 Nov;9(9):940-51. (PMID: 18991591)
J Pharmacol Exp Ther. 2012 Apr;341(1):2-15. (PMID: 22190645)
J Pharm Sci. 2011 Oct;100(10):4090-110. (PMID: 21541938)
J Pharm Sci. 2017 Sep;106(9):2678-2687. (PMID: 28238896)
Biomimetics (Basel). 2023 May 28;8(2):. (PMID: 37366821)
Clin Transl Sci. 2022 Jan;15(1):79-91. (PMID: 34080287)
Drug Metab Dispos. 2012 May;40(5):1007-17. (PMID: 22344703)
CPT Pharmacometrics Syst Pharmacol. 2024 Apr;13(4):524-543. (PMID: 38356302)
Clin Pharmacol Ther. 2021 Mar;109(3):762-771. (PMID: 32970864)
Lab Chip. 2022 Jul 26;22(15):2853-2868. (PMID: 35833849)
AAPS J. 2017 Sep;19(5):1499-1512. (PMID: 28752430)
Genes (Basel). 2020 Oct 30;11(11):. (PMID: 33143137)
Drug Metab Dispos. 2017 Jun;45(6):686-691. (PMID: 28396528)

Date Created: 20240215 Date Completed: 20240415 Latest Revision: 20240522

20240522

PMC11015085

10.1002/psp4.13110

38356302