Quantification of gastrointestinal liquid volumes and distribution following a 240 mL dose of water in the fasted state

Mudie, Deanna M.; Murray, Kathryn; Hoad, Caroline L.; Pritchard, Susan E.; Garnett, Martin C.; Amidon, Gordon L.; Gowland, Penny A.; Spiller, Robin C.; Amidon, Gregory E.; Marciani, Luca

Abstract

Previous imaging studies offered a snapshot of water distribution in fasted humans and showed that water in the small intestine is distributed in small pockets. This study aimed to quantify the volume and number of water pockets in the upper gut of fasted healthy humans following ingestion of a glass of water (240 mL, as recommended for bioavailability/bioequivalence (BA/BE) studies), using recently validated noninvasive magnetic resonance imaging (MRI) methods. Twelve healthy volunteers underwent upper and lower abdominal MRI scans before drinking 240 mL (8 fluid ounces) of water. After ingesting the water, they were scanned at intervals for 2 h. The drink volume, inclusion criteria, and fasting conditions matched the international standards for BA/BE testing in healthy volunteers. The images were processed for gastric and intestinal total water volumes and for the number and volume of separate intestinal water pockets larger than 0.5 mL. The fasted stomach contained 35 ± 7 mL (mean ± SEM) of resting water. Upon drinking, the gastric fluid rose to 242 ± 9 mL. The gastric water volume declined rapidly after that with a half emptying time (T50%) of 13 ± 1 min. The mean gastric volume returned back to baseline 45 min after the drink. The fasted small bowel contained a total volume of 43 ± 14 mL of resting water. Twelve minutes after ingestion of water, small bowel water content rose to a maximum value of 94 ± 24 mL contained within 15 ± 2 pockets of 6 ± 2 mL each. At 45 min, when the glass of water had emptied completely from the stomach, total intestinal water volume was 77 ± 15 mL distributed into 16 ± 3 pockets of 5 ± 1 mL each. MRI provided unprecedented insights into the time course, number, volume, and location of water pockets in the stomach and small intestine under conditions that represent standard BA/BE studies using validated techniques. These data add to our current understanding of gastrointestinal physiology and will help improve physiological relevance of in vitro testing methods and in silico transport analyses for prediction of bioperformance of oral solid dosage forms, particularly for low solubility Biopharmaceutics Classification System (BCS) Class 2 and Class 4 compounds.

Citation

Mudie, D. M., Murray, K., Hoad, C. L., Pritchard, S. E., Garnett, M. C., Amidon, G. L., Gowland, P. A., Spiller, R. C., Amidon, G. E., & Marciani, L. (2014). Quantification of gastrointestinal liquid volumes and distribution following a 240 mL dose of water in the fasted state. Molecular Pharmaceutics, 11(9), 3039-3047. https://doi.org/10.1021/mp500210c

• Journal Article Type: Article
• Acceptance Date: Aug 12, 2014
• Online Publication Date: Aug 12, 2014
• Publication Date: Sep 24, 2014
• Deposit Date: Aug 21, 2017
• Publicly Available Date: Feb 21, 2019
• Print ISSN: 1543-8384
• Electronic ISSN: 1543-8392
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 9
• Pages: 3039-3047
• DOI: https://doi.org/10.1021/mp500210c
• Public URL: https://nottingham-repository.worktribe.com/output/1111963
• Publisher URL: https://pubs.acs.org/doi/10.1021/mp500210c
• Related Public URLs: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84906901999&partnerID=40&md5=8870b185afae187d306503e8ca5d6dec
• Contract Date: Feb 21, 2019