In vivo Fluid Volume in Rat Gastrointestinal Tract: Kinetic Analysis on the Luminal Concentration of Non-Absorbable FITC-Dextran after Oral Administration.

Journal of Pharmaceutical Sciences(2020)

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摘要
Previously, 1 mL of purified water (hyposmotic) or saline (isosmotic) which dissolved 200 μM of FITC-dextran (FD-4), a nonabsorbable marker, was orally administered to rats, and luminal concentration-time profile of FD-4 was directly measured. In this study, at first, luminal FD-4 concentration was measured after oral administration of 0.5 mL of FD-4 purified water solution (200 μM). Then, kinetic analysis was conducted to calculate the fluid volume that passed through each segment of the gastrointestinal tract (Vfluid), based on the luminal FD-4 concentration-time profiles obtained from 3 different administration groups. In the group of 1 mL purified water administration, most of administered water was absorbed quickly from the duodenum and upper jejunum, whereas group of saline administration (1 mL) showed only a little amount of absorbed in the upper small intestine. In 0.5 mL purified water group, Vfluid in the stomach was approximately half compared to that in 1 mL purified water group. However, for small intestine, almost the same values of Vfluid were obtained regardless of the dose-volume. Our findings are valuable to improve the quality of in vitro predictive dissolution tools or in silico simulation for predicting oral drug absorption.
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关键词
fluid absorption,gastrointestinal tract,luminal concentration,luminal fluid,osmolality
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