Physiologically based pharmacokinetic (PBPK) modeling offers a unique modality to incorporate multiple levels of information to estimate age-specific pharmacokinetics. In 2012, the US Food and Drug Administration’s (FDA) Advisory Committee for Pharmaceutical Science and Clinical Pharmacology unanimously voted to support the motion that modeling and simulation be considered for all pediatric drug development programs. During the same meeting, the committee also passed the routine use of physiologically based pharmacokinetic (PBPK) modeling, when possible, be incorporated into the pediatric drug development process.
In order to increase efficiencies surrounding the pediatric drug development process, the US FDA introduced the pediatric decision tree, which delineates required clinical investigations in pediatric populations in order to comply with current legislation. The framework provides a venue by which adult efficacy data can be extrapolated to pediatrics, subsequently reducing the number of children required to participate in clinical trials. In recognition that children may display developmentally unique differences in absorption, distribution, metabolism, and excretion (ADME) and resultantly exhibit variable patterns of drug sensitivity when compared to adults, the decision tree does not permit for extrapolation of PK and safety data between adults and children. As a result, clinical assessments of pediatric PK and safety are required. Considering the integral role of PK in drug efficacy, use of pediatric PBPK models can serve to integrate multiple levels of information (i.e., in vitro, preclinical, clinical, etc.) to elucidate PK changes among children and function as a complement to pediatric clinical investigations. Estimates of age-specific PK can be utilized to support dose selection and assess for the potential for concentration-related toxicities within pediatrics.
KinderPharm uses PK–Sim® and MoBi® software platforms in performing PBPK modeling for its clients. For more about our systems visit http://www.systems-biology.com/products/pk-sim.html and http://www.ema.europa.eu/docs/en_GB/document_library/Presentation/2009/11/WC500009839.pdf
KinderPharm provides Physiologically Based Pharmacokinetic (PBPK) Modeling strategies and services to our customers to meet these US FDA guidelines. Contact us for an assessment of your Pediatric Strategy Plan to determine the best method for your pediatric drug development process.