AIM: Applying physiologically-based pharmacokinetic (PBPK) modelling in @entity5 drug development is still challenging. We aimed to demonstrate how PBPK modelling can be applied to optimize dose and sampling times for a paediatric pharmacokinetic (PK) bridging study in oncology and to compare with the allometric scaling population PK (AS-popPK) approach, using @entity1205 as an example. METHODS: A PBPK model for @entity1205 was first developed for @entity5 @entity1 using Simcyp   and subsequently used to predict its PK profiles in @entity1 by accounting for age-dependent physiological differences. Dose (mg m(-2) ) requirements for @entity1 aged 0-18 years were calculated to achieve targeted exposure in adults. Simulated data were then analyzed using population PK modelling with MONOLIX   in order to perform design optimization with the population Fisher information matrix (PFIM). In parallel, the AS-popPK approach was performed for the comparison. RESULTS: The PBPK model developed for @entity1205 adequately predicted its PK profiles in both adult and @entity5 @entity1 (predicted clearance and volume of distribution within 1.5 fold of observed data). The revised dose of @entity1205 for a @entity1 over 1.5 years old was higher than the adult dose. Considering clinical constraints, the optimal design contained two groups of 15 @entity1 , having three or four sampling times and had good predicted relative standard errors (RSE<30%) for almost all parameters. The AS-popPK approach performed reasonably well but could not predict for very young @entity1 . CONCLUSION: This research shows the clinical utility of PBPK modelling in combination with population PK modelling and optimal design to support paediatric oncology development.

Optimizing pharmacokinetic bridging studies in paediatric oncology using physiologically-based pharmacokinetic modelling: application to XXXX .

@entity5 :: ('MESH:D009369', 'Disease') :: ['paediatric cancer', 'adult cancer'] @entity1 :: ('9606', 'Species') :: ['children', 'patients', 'child'] @entity1205 :: ('MESH:C067311', 'Chemical') :: ['docetaxel']
@entity1205 :: (MESH:C067311,Chemical) :: ['docetaxel']
