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Compartmental transit and dispersion model analysis of small intestinal transit flow in humans
Affiliation:1. Simcyp Limited (a Certara company), Sheffield, UK;2. Emeritus Professor of Clinical Pharmacology, University of Sheffield, Sheffield, UK;1. University of Manchester, United Kingdom;2. AstraZeneca, United Kingdom;3. Sanofi, France;4. Simcyp Ltd, United Kingdom;5. AstraZeneca, Sweden;6. Sanofi, Germany;7. Sanofi, United States;8. Orion Pharma, Finland;9. Goethe University Frankfurt am Main, Germany;10. Novartis, United States;11. AbbVie, Germany;12. Simulations Plus, Inc., United States;13. Pfizer, United States;14. Pfizer, United Kingdom;15. Merck Sharp & Dohme (MSD), United Kingdom;p. Janssen, Belgium;q. GlaxoSmithKline, United Kingdom;r. Johannes Gutenberg University of Mainz, Germany;s. Bristol-Myers Squibb, United Kingdom;t. Uppsala University, Sweden;1. College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, United States;2. Pharmacokinetics Group, Sawai Pharmaceutical Co., Ltd., Osaka 532-0003, Japan
Abstract:The purpose of this investigation was to characterize the small intestinal transit flow in humans using quantitative and mechanistic approaches. We presented a compartmental transit model to anatomize the transit process of oral dosage forms through the human small intestinal tract. A dispersion model with constant input rate and a single-compartment model were also employed to depict the dispersion and fluid flow in the human small intestinal tract. The literature data of the small intestinal transit time were utilized to statistically construct transit flow profile. The mean small intestinal transit time in humans was found to be 199 min with a 95% confidence interval of 7 min. It was demonstrated that the small intestinal transit flow profile was well characterized by both compartmental transit and dispersion models, but not by the single-compartment model. We concluded that the compartmental transit model might be superior to the single-compartment model and less complex than the dispersion model.
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