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Mechanistic Fluid Transport Model to Estimate Gastrointestinal Fluid Volume and Its Dynamic Change Over Time

  • Research Article
  • Theme: Advances and Applications of In Vivo Medical Imaging in Drug Development and Regulation
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Abstract

Gastrointestinal (GI) fluid volume and its dynamic change are integral to study drug disintegration, dissolution, transit, and absorption. However, key questions regarding the local volume and its absorption, secretion, and transit remain unanswered. The dynamic fluid compartment absorption and transit (DFCAT) model is proposed to estimate in vivo GI volume and GI fluid transport based on magnetic resonance imaging (MRI) quantified fluid volume. The model was validated using GI local concentration of phenol red in human GI tract, which was directly measured by human GI intubation study after oral dosing of non-absorbable phenol red. The measured local GI concentration of phenol red ranged from 0.05 to 168 μg/mL (stomach), to 563 μg/mL (duodenum), to 202 μg/mL (proximal jejunum), and to 478 μg/mL (distal jejunum). The DFCAT model characterized observed MRI fluid volume and its dynamic changes from 275 to 46.5 mL in stomach (from 0 to 30 min) with mucus layer volume of 40 mL. The volumes of the 30 small intestine compartments were characterized by a max of 14.98 mL to a min of 0.26 mL (0–120 min) and a mucus layer volume of 5 mL per compartment. Regional fluid volumes over 0 to 120 min ranged from 5.6 to 20.38 mL in the proximal small intestine, 36.4 to 44.08 mL in distal small intestine, and from 42 to 64.46 mL in total small intestine. The DFCAT model can be applied to predict drug dissolution and absorption in the human GI tract with future improvements.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, 48109, USA

    Alex Yu, Yasuhiro Tsume, Mark Koenigsknecht, Gordon L. Amidon, Ann Frances, Bo Wen & Duxin Sun

  2. Department of Mathematics, College of Literature, Science, and the Arts, University of Michigan, Ann Arbor, Michigan, 48109, USA

    Trachette Jackson

  3. Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, 48109, USA

    Jeffrey Wysocki, Jason R. Baker & William Hasler

  4. Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals and the University of Nottingham, Nottingham, NG7 2UH, UK

    Luca Marciani

  5. Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, 48109, USA

    Amit Pai

  6. College of Pharmacy, Tianjin Medical University, Tianjin, People’s Republic of China

    Duxin Sun

  7. College of Pharmacy, The University of Michigan, North Campus Research Complex (NCRC), Room 3353, Building 520,1600 Huron Parkway, Ann Arbor, Michigan, 48109, USA

    Duxin Sun

Authors
  1. Alex Yu
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  2. Trachette Jackson
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  3. Yasuhiro Tsume
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  4. Mark Koenigsknecht
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  5. Jeffrey Wysocki
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  6. Luca Marciani
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  7. Gordon L. Amidon
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  8. Ann Frances
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  9. Jason R. Baker
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  10. William Hasler
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  11. Bo Wen
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  12. Amit Pai
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  13. Duxin Sun
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Corresponding author

Correspondence to Duxin Sun.

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Ethics Statement

The study was approved by University of Michigan IRBMED HUM00085066 and the Food and Drug Administration (RIHSC protocol 14-029D. Study volunteers provided written informed consent. The study was in accordance with study protocol, the International Conference on Harmonization of Good Clinical Practice guidelines, and applicable local regulatory requirements. The ClinicalTrials.gov identifier is NCT02806869.

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Guest Editors: Peng Zou, Doanh Tran, and Edward Bashaw

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Yu, A., Jackson, T., Tsume, Y. et al. Mechanistic Fluid Transport Model to Estimate Gastrointestinal Fluid Volume and Its Dynamic Change Over Time. AAPS J 19, 1682–1690 (2017). https://doi.org/10.1208/s12248-017-0145-x

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  • DOI: https://doi.org/10.1208/s12248-017-0145-x

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