In vivo models for lactation studies

The informed decisions to suspend or continue breastfeeding require evidence of how much of a particular chemical compound transfers to milk, and in turn the newborns. The ConcePTION in vivo model is part of a non-clinical framework to support data generation relying on three pillars. The model is designed to verify the in vitro results on milk transfer. Together, these two models inform and verify PBPK (in silico) models.

The non-clinical framework and in vivo model can inform the scientific community and society on the amounts of maternal medicines that can be found in mother’s milk and the newborn’s blood (or other biological samples).

The ConcePTION in vivo model has been developed in lactating Göttingen Minipig sows. The use of the minipig in in vivo studies is the most comprehensive way to obtain quantitative data to make a relevant assessment of the exposure of a maternal medicine in the milk and thus, a meaningful prediction of its concentrations in human breast milk along with systemic medicine exposure in breastfed infants. The in vivo model also enables the generation of maternal systemic PK data and maternal milk drug concentrations. Further, infant systemic drug concentrations due to exposure via the milk can be determined and together, these data can allow for the determination of a relative infant dose. 

In addition to the in vivo models, the ConcePTION non-clinical framework for lactation studies includes in vitro models and in silico (PB/PK) models. The project has also developed a framework for clinical lactation studies.

Publications

Bernardini, C., Nesci, S., La Mantia, D., Salaroli, R., Nauwelaerts, N., Ventrella, D., Elmi, A., Trombetti, F., Zannoni, A. & Forni, M. Isolation and characterization of mammary epithelial cells derived from Göttingen Minipigs: A comparative study versus hybrid pig cells from the IMI-ConcePTION Project, Research in Veterinary Science, Volume 172, June 2024. DOI: 10.1016/j.rvsc.2024.105244

Armoudjian, Y., Lin, A., Lammens, B., Van Daele, J., Annaert, P. (2023) Sensitive and rapid method for the quantitation of amoxicillin in minipig plasma and milk by LC-MS/MS: A contribution from the IMI ConcePTION project, Journal of Pharmacological and Toxicological Methods, 107264. DOI: 10.1016/j.vascn.2023.107264.

Bernardini, C., La Mantia, D., Salaroli, R., Zannoni, A., Nauwelaerts, N., Deferm, N., Ventrella, D., Bacci, M.L., Sarli, G., Bouisset-Leonard, M., Annaert, P., Forni, M. (2021). Development of a Pig Mammary Epithelial Cell Culture Model as a Non-Clinical Tool for Studying Epithelial Barrier — A Contribution from the IMI-ConcePTION Project. Animals, vol 11(7). DOI: 10.3390/ani11072012

Ventrella, D., Ashkenazi, N., Elmi, A., Allegaert, K., Aniballi, C., DeLise, A., Devine, P.J., Smits, A., Steiner, L., Forni, M., Bouisset-Leonard, M., Bacci, M.L. (2021). Animal Models for In Vivo Lactation Studies: Anatomy, Physiology and Milk Compositions in the Most Used Non-Clinical Species: A Contribution from the ConcePTION Project. Animals, 11(3), 714. DOI: 10.3390/ani11030714

Public reports