Applying PBPK Modeling to Predict Drug Exposure in Special Populations

This chapter will explore strategies for building PBPK models for special populations. In recent years, a significant increase in PBPK modeling applications has been observed with a growing interest in predicting pharmacokinetics (PK) in special populations. PBPK modeling offers the opportunity to study the PK for populations for which clinical trials might not be conducted; therefore, this tool promises to revolutionize drug development and personalized medicine. Building a PBPK model for special populations requires a profound understanding of patient-specific physiology and anatomy. This chapter will illustrate the process of building and applying a PBPK model in special populations such as pediatric, cystic fibrosis, and down syndrome patients. The application of PBPK modeling will be demonstrated by highlighting published literature examples. These examples elucidate the importance of developing complex in vitro experiments (e.g., patient-specific biorelevant dissolution tests or use of microphysiological systems (MPS) and organoids) for gathering information on dissolution, absorption, transport, metabolism, and toxicity to inform models. Finally, conducting high-quality research to better characterize the physiology of special populations will help culminate the current gaps and propel the advancement of existing PBPK models.