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

Yu, Alex; Jackson, Trachette; Tsume, Yasuhiro; Koenigsknecht, Mark; Wysocki, Jeffrey; Marciani, Luca; Amidon, Gordon L.; Frances, Ann; Baker, Jason R.; Hasler, William; Wen, Bo; Pai, Amit; Sun, Duxin

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.

Citation

Yu, A., Jackson, T., Tsume, Y., Koenigsknecht, M., Wysocki, J., Marciani, L., …Sun, D. (2017). Mechanistic Fluid Transport Model to Estimate Gastrointestinal Fluid Volume and Its Dynamic Change Over Time. AAPS Journal, 19(6), 1682-1690. https://doi.org/10.1208/s12248-017-0145-x

• Journal Article Type: Article
• Acceptance Date: Sep 1, 2017
• Online Publication Date: Oct 4, 2017
• Publication Date: 2017-11
• Deposit Date: Dec 13, 2018
• Publicly Available Date: Dec 20, 2018
• Journal: The AAPS Journal
• Electronic ISSN: 1550-7416
• Publisher: American Association of Pharmaceutical Scientists
• Peer Reviewed: Peer Reviewed
• Volume: 19
• Issue: 6
• Pages: 1682-1690
• DOI: https://doi.org/10.1208/s12248-017-0145-x
• Public URL: https://nottingham-repository.worktribe.com/output/1412064
• Publisher URL: https://link.springer.com/article/10.1208%2Fs12248-017-0145-x
• Additional Information: This is a post-peer-review, pre-copyedit version of an article published in AAPS Journal. The final authenticated version is available online at: http://dx.doi.org/10.1208/s12248-017-0145-x
• Contract Date: Dec 20, 2018