Oral drug absorption in pediatrics: the intestinal wall, its developmental changes and current tools for predictions

Area of Science:

• Pharmacology
• Pediatric Medicine
• Drug Metabolism

Background:

• Drug absorption and metabolism are influenced by physiological and biochemical factors.
• These factors exhibit age-related differences between children and adults, impacting drug exposure and response.
• Pediatric drug dosage optimization is necessary to ensure therapeutic efficacy and minimize adverse effects.

Purpose of the Study:

• To review current knowledge on developmental changes affecting intestinal drug absorption and presystemic metabolism.
• To discuss experimental and modeling approaches for studying pediatric pharmacokinetics.
• To highlight existing knowledge gaps and challenges in pediatric drug development.

Main Methods:

• Literature review of developmental changes in intestinal drug absorption and metabolism.
• Discussion of experimental techniques used to study pediatric pharmacokinetics.
• Exploration of physiologically based pharmacokinetic (PBPK) modeling.

Main Results:

• Significant age-related variations exist in gastrointestinal physiology and biochemistry impacting drug disposition.
• Ethical constraints and limited predictive models complicate pediatric pharmacokinetic studies.
• PBPK modeling offers a promising, albeit challenging, approach to predict pediatric drug behavior.

Conclusions:

• Understanding age-dependent changes in intestinal drug handling is critical for pediatric pharmacotherapy.
• Further development of predictive preclinical and in vitro models is needed.
• Addressing knowledge gaps will improve the safe and effective use of medications in children.