Drug Screening, Oral Bioavailability and Regulatory Aspects: A Need for Human Organoids
Abstract
:1. Introduction
2. Bioavailability and the Intestinal Epithelium
2.1. Anatomy and Function of the Intestinal Epithelium
2.2. Presystemic Luminal Drug Metabolism
3. Intestinal Nutrient and Drug Transport
3.1. Intestinal Nutrient Absorption
3.2. Intestinal Transporters and Drug Uptake
3.3. Intestinal Ion Pumps
4. Intestinal Epithelial Cell Metabolism
5. Currently Used Models
5.1. Cell Lines
5.2. Other Models
6. Human Intestinal Organoids and How They Can Improve Drug Screening
6.1. Properties of Intestinal Organoids
6.2. Intestinal Organoids to Assess Nutrient and Drug Uptake
6.3. Current and Future Strategies for Organoids in Pharmacological Research
7. Regulatory Aspects
8. Future Directions
9. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Abbreviations
ADME | (Drug) Absorption, Distribution, Metabolism, and Excretion |
ECVAM | European Centre for the Validation of Alternative Methods |
FDA | U.S. Food and Drug Administration |
HTS | High-Throughput Screening |
IECs | Intestinal Epithelial Cells |
JRC | Joint Research Centre |
MOC | Multi-Organ Chip |
MPS | MicroPhysiological System |
NAMs | New Approach Methods |
NAT | Non-Animal Methods |
OOC | Organ-On-a-Chip |
PAMPA | Parallel Artificial Membrane Permeability Assay |
PBKD | Physiologically Based Kinetic and Dynamic |
QSAR | Quantitative Structure-Activity Relationship |
VCBA | Virtual Cell Based Assay |
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Failure Rate | No of Drugs Tested | Years | Reference |
---|---|---|---|
81–84% | 1.738 | 1993–2004 | DiMasi et al., 2010 [125] |
88.6% | >9.200 | 1996–2014 | Smietana et al., 2016 [126] |
86.2% | 21.143 | 2000–2015 | Wong et al., 2019 [127] |
90–95% | >850 | 2002–2008 | Arrowsmith, 2012 [113] |
89.6% | >7.300 | 2003–2011 | Hay et al., 2014 [128] |
90.4% | 7.455 | 2006–2015 | Thomas et al., 2016 [129] |
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Zietek, T.; Boomgaarden, W.A.D.; Rath, E. Drug Screening, Oral Bioavailability and Regulatory Aspects: A Need for Human Organoids. Pharmaceutics 2021, 13, 1280. https://doi.org/10.3390/pharmaceutics13081280
Zietek T, Boomgaarden WAD, Rath E. Drug Screening, Oral Bioavailability and Regulatory Aspects: A Need for Human Organoids. Pharmaceutics. 2021; 13(8):1280. https://doi.org/10.3390/pharmaceutics13081280
Chicago/Turabian StyleZietek, Tamara, Wolfgang A. D. Boomgaarden, and Eva Rath. 2021. "Drug Screening, Oral Bioavailability and Regulatory Aspects: A Need for Human Organoids" Pharmaceutics 13, no. 8: 1280. https://doi.org/10.3390/pharmaceutics13081280
APA StyleZietek, T., Boomgaarden, W. A. D., & Rath, E. (2021). Drug Screening, Oral Bioavailability and Regulatory Aspects: A Need for Human Organoids. Pharmaceutics, 13(8), 1280. https://doi.org/10.3390/pharmaceutics13081280