Generic PBPK template for predicting drug concentration time profiles in human breast milk

Task 34 Development of a robust PBPK framework to predict drug concentration profiles in human breast milk M13M37 KUL GSK BioNotus UNIBO CHUT NVS Teva CHUVDrugspecific clearance values for excretion into milk will be generated with the in vitro and in vivo models developed in Tasks 32 and 33 along with previously generated in vitroin vivo data111216 and eventually coming from EFPIA partners will be used to feed drugspecific PBPK models Based on these models a generic PBPK template will be developed that encompasses milk excretion of drugs The PBPK models will be developed in an industrysupported platform eg Simcyp from Certara while the utility and added value of alternative platforms will be explored Using the results of a second set of in vitro experiments see Task 32 as input data the predictive performance of the developed PBPK modelling strategy will be thoroughly evaluated This will be achieved by comparing PBPKbased predictions with clinical observations In case adequate in vivo data are available eg regarding systemic maternal exposure for existing drugs a retrograde approach will be used Possible covariates identified with population PK approaches in WP4 will be used to further improve the developed PBPK models