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

ABSTRACT:

Aim

Applying physiologically-based pharmacokinetic (PBPK) modelling in paediatric cancer 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 docetaxel as an example.

Methods

A PBPK model for docetaxel was first developed for adult cancer patients using Simcyp® and subsequently used to predict its PK profiles in children by accounting for age-dependent physiological differences. Dose (mg m(-2) ) requirements for children aged 0-18 years were calculated to achieve targeted exposure in adults. Simulated data were then analyzed using population PK model

SUBMITTER: Thai HT 

PROVIDER: S-EPMC4574838 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature