Magnetic Resonance Imaging Quantification of Gastrointestinal Liquid Volumes and Distribution in the Gastrointestinal Tract of Children

Abstract

The volume and localisation of fluid in the paediatric gastro-intestinal tract is crucial to inform the design of in vitro and in silico models that predict the absorption of oral drugs administered to children. Previous studies have used magnetic resonance imaging (MRI) to quantify fluid volumes and localisation in the intestines of adults; this study is the first to undertake similar analysis of paediatric participants. This study quantified the amount and distribution of fluid in fasted and fluid-fed children using MRI data captured during routine clinical assessment. Data from 32 fasted children (aged 0-16 years) and 23 fluid-fed (aged 8-16 years) was evaluated. The gastric volume ranged from 0-9mL in the fasted and 19-423mL in the fluid-fed state. The small intestinal volume was recorded to be 0-51mL in the fasted and 6-91mL in the fluid-fed state with an average number of 7.7 and 22.4 fluid pockets respectively. The data showed significant differences in gastric volumes and the number of fluid pockets in the small intestine for age-matched fasted and fluid-fed children (p<0.05). Both the number and the volume of pockets reported in children are much lower than those previously reported in adults. This study is the first to report intestinal volumes and localisation in children and provides new information to inform the design of biorelevant in vitro models and real values to update in silico models. The availability of data from both fluid-fed and fasted children show the extremes of fluid volumes that are present in the gastro-intestinal tract which is useful to understand the variability associated with drug absorption in children.

Quantification of Fluid Volume and Distribution in the Paediatric Colon via Magnetic Resonance Imaging

“…Horos is an open-source code software program distributed free of charge under the LGPL license at Horosproject.org and sponsored by Nimble Co LLC d/b/a Purview in Annapolis, MD, USA. Fluid identification within the MRI slices was based on the intensity of cerebrospinal fluid (CSF) which is routine in interpretation of these images [ 3 , 4 , 31 , 42 , 45 ]. The average voxel intensity within the CSF was used as threshold value for free fluid.…”

“…Despite the clear advantages of oral formulations, such preparations rely on drug liberation and dissolution for absorption. The free water available at the site of dissolution is a critical parameter for these processes as it also affects local drug concentration and thus permeation [ 3 , 4 , 5 ]. As such, a comprehensive understanding of the amount and distribution of fluid throughout the gastrointestinal tract (GIT) is required to ensure appropriate and adequate absorption of oral medicines [ 6 ].…”

Development of a Pediatric Relative Bioavailability/Bioequivalence Database and Identification of Putative Risk Factors Associated With Evaluation of Pediatric Oral Products

“…The intrinsic poor solubility of certain drugs can increase risks of non-linear PK due to incomplete dissolution within the GI tract (35,49,52,63), especially for children whose GI volume is less compared to adults (93).…”

Enteral Medication for the Tube‐Fed Patient: Making This Route Safe and Effective

“…There is still considerable variability in gastric emptying even in the fasted state, depending on gastric fluid volume and phase of the interdigestive migrating myoelectric complex. The volume, as well as the composition, of fluid in the intestine varies not only between the fed and fasted states but also in the number and distribution of discontinuous fluid pockets found throughout the gut lumen 13,14,15 …”

“…The volume, as well as the composition, of fluid in the intestine varies not only between the fed and fasted states but also in the number and distribution of discontinuous fluid pockets found throughout the gut lumen. 13,14,15 Commercial oral drug products are designed with all of the above in mind. Therefore, crushing and/or dispersing solids in minimal fluid prior to administration by EAD, especially in patients with altered physiology, can significantly change the intended therapeutic effect of the original drug design.…”