Model-Informed Drug-Drug Interaction Assessment in Pediatric Populations

Drug-drug interactions (DDIs) are a critical concern in pediatric medicine, but current methodologies for assessing these interactions are often limited. Pediatric populations exhibit significant physiological differences compared to adults, including variations in drug absorption, distribution, metabolism, and excretion (ADME) that can affect drug interactions. In addition, only limited data could be available for the age-appropriate formulation. As a result, the common practice of extrapolating adult DDI data to pediatric patients may not be accurate, leading to potential therapeutic failures or adverse effects. This challenge has highlighted the need for innovative approaches to DDI prediction and safer pediatric drug development.
One such approach is Physiologically Based Pharmacokinetic (PBPK) modeling, a powerful tool that integrates detailed physiological data to predict how drugs behave within the human body. PBPK modeling incorporates age-specific physiological parameters, such as body size, organ function, and enzyme activity, to simulate the PK of drugs in pediatric populations. This allows for more precise DDI predictions, even when clinical data for children are scarce or unavailable.

This symposium will explore how PBPK modeling is transforming the way we assess DDIs in pediatric populations. We will start with an overview of how PBPK models are constructed, emphasizing the integration of age-specific factors and their relevance for assessing drug interactions in children. The symposium will highlight real-world examples where PBPK modeling has been successfully used to assess DDIs in pediatric populations. Case studies will demonstrate the model's effectiveness in predicting potential interactions and guiding safer drug combinations. For example, we will examine how PBPK modeling has been applied to commonly used pediatric medications, offering attendees a clear understanding of how it improves the accuracy of DDI predictions. The issues related to data availability, model validation, and the complexity of pediatric drug metabolism will be discussed. Regulatory perspectives will also be discussed, highlighting how agencies like the FDA and EMA are incorporating PBPK models into their drug approval processes for pediatric indications.

Finally, the symposium will explore future directions in pediatric DDI research, including the integration of genetic data, disease state modeling, and the potential for personalized medicine. As we move toward more individualized treatment strategies, PBPK modeling will play a pivotal role in ensuring that pediatric patients receive the safest and most effective therapies.