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

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 168μg/mL (stomach), to 563μg/mL (duodenum), to 202μg/mL (proximal jejunum), and to 478μg/mL (distal jejunum). The DFCAT model characterized observed MRI fluid volume and its dynamic changes from 275 to 46.5mL in stomach (from 0 to 30min) with mucus layer volume of 40mL. The volumes of the 30 small intestine compartments were characterized by a max of 14.98mL to a min of 0.26mL (0-120min) and a mucus layer volume of 5mL per compartment. Regional fluid volumes over 0 to 120min ranged from 5.6 to 20.38mL in the proximal small intestine, 36.4 to 44.08mL in distal small intestine, and from 42 to 64.46mL in total small intestine. The DFCAT model can be applied to predict drug dissolution and absorption in the human GI tract with future improvements.