Development, characterization and validation of an in vitro/in silico platform to predict transfer of medicines to human breast milk along with neonatal systemic exposure to maternal medication.

Breastfeeding has been shown to have short- and long-term benefits regarding chronic diseases, cognitive deficits, infant morbidity and mortality. However, breastfeeding adherence in the EU is low. One of the factors leading to the decision not to breastfeed is the lack of safety information for medicines. It is currently impossible to make evidence-based decisions on the use of maternal medication during breastfeeding. Women are counselled not to breastfeed while on medication or to postpone the therapy in favour of breastfeeding. The aim of this PhD project is the development and application of a robust non-clinical toolbox for the quantitative determination of medicine transport into human breastmilk. To achieve this goal, in vitro models for the blood/milk barrier will be developed, characterized, validated and applied to therapeutically relevant model compounds. Extrapolation of the obtained in vitro data will enable the development of physiologically-based pharmacokinetic (PBPK) models to predict secretion of medicines to human breast. These PBPK models will then be extended to predict systemic exposure to maternal medication in breastfeeding infants. After validation, regulatory approval of the developed non-clinical tools will be pursued. The outcome of this project will enable a new paradigm in evidence-based risk assessment regarding medication use by breastfeeding women and their babies. The beneficial health and economic impact cannot be overestimated.