Regulatory experience with physiologically based pharmacokinetic modeling for pediatric drug trials.

Physiologically based pharmacokinetic (PBPK) approaches that incorporate the developmental physiology and ontogeny of cytochrome P450 (CYP) enzymes may have value in the design of pediatric trials. Four recent submissions to the US Food and Drug Administration (FDA) incorporated different PBPK applications to pediatric drug development.Further testing of PBPK models for three drugs showed that these models generally under predicted drug clearance. PBPK modeling may have potential for improving pediatric trials through the learn-and-confirm approaches utilized in current regulatory submissions.