Increasing application of pediatric physiologically based pharmacokinetic models across academic and industry organizations

Abstract There has been a significant increase in the use of physiologically based pharmacokinetic (PBPK) models during the past 20 years, especially for pediatrics. The aim of this study was to give a detailed overview of the growth and areas of application of pediatric PBPK (P‐PBPK) models. A total of 181 publications and publicly available regulatory reviews were identified and categorized according to year, author affiliation, platform, and primary application of the P‐PBPK model (in clinical settings, drug development or to advance pediatric model development in general). Secondary application areas, including dose selection, biologics, and drug interactions, were also assessed. The growth rate for P‐PBPK modeling increased 33‐fold between 2005 and 2020; this was mainly attributed to growth in clinical and drug development applications. For primary applications, 50% of articles were classified under clinical, 18% under drug development, and 33% under model development. The most common secondary applications were dose selection (75% drug development), pharmacokinetic prediction and covariate identification (47% clinical), and model parameter identification (68% model development), respectively. Although population PK modeling remains the mainstay of approaches supporting pediatric drug development, the data presented here demonstrate the widespread application of P‐PBPK models in both drug development and clinical settings. Although applications for pharmacokinetic and drug–drug interaction predictions in pediatrics is advocated, this approach remains underused in areas such as assessment of pediatric formulations, toxicology, and trial design. The increasing number of publications supporting the development and refinement of the pediatric model parameters can only serve to enhance optimal use of P‐PBPK models.