Gastrointestinal Fluid Volumes in Pediatrics: A Retrospective MRI Study

Abstract

The volume and distribution of fluids available in the gastrointestinal (GI) tract may substantially affect oral drug absorption. Magnetic resonance imaging (MRI) has been used in the past to quantify these fluid volumes in adults and its use is now being extended to the pediatric population. The present research pursued a retrospective, explorative analysis of existing clinical MRI data generated for pediatric patients. Images of 140 children from all pediatric subpopulations were analyzed for their resting GI fluid volumes in fasting conditions. In general, an increase in fluid volume as a function of age was observed for the stomach, duodenum, jejunum, and small intestine (SI) as a whole. No specific pattern was observed for the ileum and colon. Body mass index (BMI), body weight, body height, and SI length were evaluated as easy-to-measure clinical estimators of the gastric and SI fluid volumes. Although weight and height were identified as the best estimators, none performed ideally based on the coefficient of determination (R2). Data generated in this study can be used as physiologically relevant input for biorelevant in vitro tests and in silico models tailored to the pediatric population, thereby contributing to the efficient development of successful oral drug products for children.

Investigating Tacrolimus Disposition in Paediatric Patients with a Physiologically Based Pharmacokinetic Model Incorporating CYP3A4 Ontogeny, Mechanistic Absorption and Red Blood Cell Binding

“…The fluid volume used in the in vitro setup was set at 50 mL for adults, based on a measured average small intestinal fluid volume (SIFV) of 43 mL [ 22 ]. For the paediatric population, in vitro fluid volumes were chosen based on the average SIFV measured by Van der Veken et al [ 23 ]. A summary of the dissolution conditions can be found in Table 1 .…”

“…This sensitivity analysis was performed for both crystalline and formulated tacrolimus by fitting different solubilisation ratios to the experimentally determined solubilities in Gastroplus. For the sensitivity analysis, the baseline, minimum, and maximum values were chosen as the average, lowest, and highest SIFV measured by Van der Veken et al [ 23 ], respectively. Other Gastroplus input parameters were the same as those used in the SimCYP model but no distribution or elimination parameters were necessary; only the fraction absorbed was investigated.…”

Correction: Van der Veken et al. Gastrointestinal Fluid Volumes in Pediatrics: A Retrospective MRI Study. Pharmaceutics 2022, 14, 1935

“…In the original publication [ 1 ], there was a mistake in Figure 5 as published. The corrected Figure 5 caption appears below.…”

“…In the original publication [1], there was a mistake in Figure 5 [13,14,17,[20][21][22]26,[32][33][34][35][36][37][38][39][40][41][42][43][44].…”

Characterization of neonatal and infant enterostomy fluids - part II: Drug solubility

“…Despite significant progress in the predictive in vitro and in silico simulation of drug absorption in preclinical drug development, physiological changes related to disease, medication or age are currently poorly implemented due to the lack of reference data 13 . To advance the development of oral drugs tailored to the paediatric population 14,15 , for instance, recent studies have explored different absorption-related aspects of the gastrointestinal physiology in children, including fluid volume 16,17 , fluid composition 18,19 , and drug transporter and metabolic enzyme ontogeny 20,21 . In addition, Maharaj Pagina 3 van 28 et al 22 designed neonatal and pediatric SIF to explore drug solubility in children.…”