Physiologically based pharmacokinetic (PBPK) modeling holds great promise for anticipating the quantitative changes of pharmacokinetics in pediatric populations relative to adults, which has served as a useful tool in regulatory reviews.Although the availability of specialized software for PBPK modeling has facilitated the widespread applications of this approach in regulatory submissions,challenges in the implementation and interpretation of pediatric PBPK models remain great, for which controversies and knowledge gaps remain regarding neonatal development of the gastrointestinal tract.The commentary highlights the similarities and differences in the gastrointestinal pH and transit time between neonates and adults from a PBPK modeling prospective.Understanding the similarities and differences in these physiological parameters governing oral absorption would promote good practice in the use of pediatric PBPK modeling to assess oral exposure and pharmacokinetics in neonates.