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In Vitro and In Vivo Approaches to Determine Intestinal Epithelial Cell Permeability
Published on: October 19, 2018
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Human in vivo regional intestinal permeability: quantitation using site-specific drug absorption data
Erik Sjögren1, David Dahlgren1, Carl Roos1
1Department of Pharmacy, Biopharmaceutic Research Group, Uppsala University, SE-751 23 Uppsala, Sweden.
Molecular Pharmaceutics
|April 29, 2015
Summary
This study introduces a novel deconvolution method to indirectly estimate regional intestinal permeability (Peff) in humans. The approach accurately predicts drug absorption across different intestinal regions, aiding pharmaceutical development.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Gastrointestinal Physiology
- Pharmaceutical Sciences
Background:
- Regional intestinal permeability is crucial for pharmaceutical product development.
- Accurate in vivo estimation of site-specific intestinal effective permeability (Peff) in humans is challenging.
- Existing methods for regional Peff determination are limited.
Purpose of the Study:
- To present and evaluate a deconvolution-based approach for the indirect estimation of site-specific in vivo intestinal effective permeability (Peff) in humans.
- To generate a comprehensive dataset of human regional intestinal permeability values for various drugs.
- To assess the utility of this method in improving gastrointestinal absorption predictions for drug development.
Main Methods:
- Collected and analyzed plasma concentration-time profiles from 15 clinical studies involving regional drug administration.
- Calculated intestinal absorption rates via deconvolution using historical intravenous data.
- Estimated Peff using absorption rates, intestinal surface area, and remaining luminal dose.
Main Results:
- Generated 43 new Peff values for 14 active pharmaceutical ingredients across proximal small intestine, distal small intestine, and large intestine.
- Demonstrated a strong correlation (r² = 0.96) between indirectly estimated and directly measured jejunal Peff values.
- Observed that distal small intestine and large intestine Peff were 90% and 40% of proximal small intestine Peff, respectively.
Conclusions:
- The evaluated deconvolution method is suitable for indirectly estimating regional intestinal Peff in humans.
- This study provides the first extensive dataset of human regional intestinal permeability.
- The generated biopharmaceutical data can enhance the accuracy of gastrointestinal absorption predictions in drug development.
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