Pediatric biopharmaceutics: translating gastrointestinal characteristics into improved predictive absorption tools.

Until recently, pharmaceutical companies have never been encouraged to perform clinical studies in the pediatric population; as a result, off-label use of drugs in children is still common. Regulatory authorities have recognized this problem and have introduced incentives and requirements for the pharmaceutical industry to include pediatric studies in their development programs. An efficient drug development process is guided by reliable experimental tools that are predictive for the in vivo situation. While significant progress has been made in creating in vitro and in silico models that offer reliable information about the disposition of orally administered drugs in adults, the development of pediatric predictive models is running behind due to the limited availability of data on pediatric gastrointestinal physiology. During childhood, many physiological changes occur affecting drug pharmacokinetics. This research proposal aims to boost current knowledge of intestinal drug disposition in the pediatric population. This will be accomplished by performing a high-level characterization of the gastrointestinal environment, including developmental changes in gastrointestinal fluid composition and volume, and in the expression of drug transporters and metabolizing enzymes. These crucial data on pediatric physiology will be used to optimize in vitro and in silico models that are predictive for the in vivo performance of drug formulations in children.