TABLE 1

Summary of PBPK modeling applications in pediatric oncology drug development

DrugRoute of AdministrationObjective(s)SoftwareData Used in Model BuildPerformed Prior to FTPaReference
Busulfani.v.Predict plasma concentration-time curvesPK-Sim (Bayer Technology Services, Germany)AdultNoDiestelhorst et al., 2014
Cisplatini.v.Describe the PBPK model development; simulate cisplatin disposition in humansNot reportedDogNoEvans et al., 1982
Docetaxeli.v.Demonstrate how PBPK modeling can be applied to optimize dose and sampling times for a pediatric PK bridging study in oncologySimcyp (Certara, UK)AdultNoThai et al., 2015
Etoposidei.v.Evaluate the ability of PBPK to predict the systemic drug exposure in children and the effect of comedicationsPK-SimAdultKersting et al., 2012
Imatinibp.o.Predict plasma concentration-time profiles in plasma and tissue in pediatric subjects, and assess the effect of pediatric growth processes using a PBPK modelNot reportedAdultNoEuropean Medicines Agency, 2013
Evaluate factors influencing imatinib exposure in pediatric patients
6-Mercaptopurinei.v. and p.o.Improve dose individualization and dosage regimen optimization; model DDI interaction with methotrexateMATLAB (Mathworks, Natick, MA)AdultNoOgungbenro et al., 2014b
Methotrexatei.v. and p.o.Evaluate the role of modeling and simulation in the development of drugs for rare diseasesMATLABAdultNoOgungbenro et al., 2014a
Methotrexatei.v.Evaluate the effect of malignant effusions on the PK of methotrexateBerkeley Madonna (University of California–Berkeley, Berkeley, CA)AdultNoLi and Gwilt, 2002
Obatoclaxi.v.Evaluate the potential to achieve target exposures in infantsPK-SimMouseYesBarrett et al., 2011
Pinometostati.v.First-time-in-pediatrics starting dose selectionSimcypAdultYesWaters et al., 2014
Tazemetostatp.o.First-time-in-pediatrics starting dose selectionGastroPlus (Simulations Plus, Lancaster, CA)AdultYesRioux et al., 2015