Review of paediatric gastrointestinal physiology relevant to the absorption of orally administered medicines

Usefulness of the Beagle Model in the Evaluation of Paracetamol and Ibuprofen Exposure after Oral Administration to Pediatric Populations: An Exploratory Study

“…Therefore, data from bioavailability studies in adults are often extrapolated to the pediatric population of interest. − In line, a recent draft guideline from the U.S. Food and Drug Administration (FDA) suggested that the sponsor should perform a food effect (FE) study in adults with the pediatric formulation and that “the sponsor can use foods and quantities of food that are commonly consumed with drugs in a particular pediatric population (e.g., formula for infants)” . Recent literature review highlighted the different food effect observations between studies performed in healthy adult volunteers in comparison to food effects observed in infants/young children who were administered the same drug. , The discrepancy in the food effect outcomes could be attributed to several factors: age-dependent physiology differences, inconsistent protocols between adult and pediatric food effect studies, and age-appropriate meals chosen for each study population (standard breakfast in adults and milk-based meals in pediatric populations). ,, A dedicated investigation of the factors affecting oral absorption of pediatric formulations in the presence of standard solid–liquid meals or infant milk-based feed in adult healthy volunteers revealed that food effects for infant formulations might not be adequately evaluated when applying common adult FE study protocols …”

“…2,5 The discrepancy in the food effect outcomes could be attributed to several factors: age-dependent physiology differences, inconsistent protocols between adult and pediatric food effect studies, and age-appropriate meals chosen for each study population (standard breakfast in adults and milk-based meals in pediatric populations). 2,5,6 presence of standard solid−liquid meals or infant milk-based feed in adult healthy volunteers revealed that food effects for infant formulations might not be adequately evaluated when applying common adult FE study protocols. 5 Furthermore, as pediatric product development usually commences during the clinical stages of adult drug product development, pediatric formulation development and the food effect evaluation are mainly guided by the knowledge gained throughout adult formulation investigations and the relevant applied protocols for adults.…”

Vehicles for Drug Administration to Children: Results and Learnings from an In-Depth Screening of FDA-Recommended Liquids and Soft Foods for Product Quality Assessment

“…When co-administered with vehicles with a high fat content, poorly water-soluble lipophilic drugs may (partly) dissolve in components of the dosing vehicle, whereas in pure water, they often may not dissolve at all [24,26]. This could be associated with altered bioavailability, especially in very young children in which the resting volumes of gastric and small intestinal fluid are still relatively small and thus the volume and composition of the co-administered vehicle may have, at least temporarily, a much stronger impact on intraluminal conditions than in older children [11].…”

“…If one now assumes a very young infant, for example, administration is made to a patient in which the dimensions of the gastrointestinal tract are still very different from those of a school child or adolescent. Since especially in young infants both gastric capacity and the amount of fasted resting gastric fluid are much smaller than in older children [11], one can imagine that even a small amount of vehicle may be sufficient to alter the gastric environment and to some extent temporarily might also affect intraluminal conditions in the small intestine, increasing the likelihood of changes in the in vivo performance of the drug product. To avoid such undesired effects, only those liquids and/or soft foods that have been shown not to alter the performance of the drug product and which are considered well tolerated and suitable for use in the targeted patient populations should be considered as vehicles for that specific drug product [10].…”

Establishing Novel Doxorubicin-Loaded Polysaccharide Hydrogel for Controlled Drug Delivery for Treatment of Pediatric Brain Tumors

“…Chemotherapies administered orally and intravenously are part of the standard of care treatment for most pediatric tumors, with pediatric patients diagnosed with medulloblastoma treated with mostly, if not only, chemotherapy [2][3][4]. Sadly, barriers to the systemic route of administration limit drug penetration in the tumor microenvironment and include but are not limited to plasma protein binding, the blood-brain barrier, and structural and mechanical components within the tumor microenvironment all hindering the potential of therapeutic effect on the cancer cells [5][6][7][8]. In treating brain tumors, nearly 98% of small molecules and 100% of large molecules do not cross the blood-brain barrier, defining the blood-brain barrier as the most significant physical obstacle to treating brain tumors [9,10].…”