PBPK modelling is used to predict the concentration of different drug compounds in blood plasma and breastmilk. The method is useful in drug development, as it optimises dosing regimens and gives an idea regarding the safety of the medicine. To do so effectively researchers need data on how different drug compounds move through the body. But we don’t know enough about the physiology of new mothers and their babies. A recent ConcePTION publication highlights the challenges of developing PBPK models for these groups.
Different populations have different physiology, and data about the specific physiology of postpartum and lactating women as well as infants are poorly standardised and scattered.
“The knowledge that does exist is limited and fragmented and often, we have to work with assumptions. To be able to use physiologically based pharmacokinetic modelling to close the knowledge gap about medicine safety in breastfeeding, we need physiological data to be collected – and we need to do so systematically,” says Martje Van Neste, MD and PhD candidate at KU Leuven, and one of the authors of the publication.
Not only are postpartum weight retention, milk intake and composition and the specific physiology of breastfed infants poorly mapped. There is a consensus among academia, pharma industry and regulatory agencies that PBPK-modelling is a good tool to reduce the number of participants needed in the early phases of clinical trials. But to fully utilize the tool for the vulnerable population of postpartum and lactating women and their breastfeeding infants, there are challenges to overcome.
According to the authors, systematic searches and data standardisation are crucial to ensure that future data collection adequately reflects the different variations in physiology and minimize bias created by methodological differences in clinical studies. And to ensure essential physiological data, or subpopulations, aren’t lost because of limited or incomplete literature searches when developing these postpartum, lactation and infant PBPK-models.
By Anna Holm Bodin
Van Neste, M., Bogaerts, A., Nauwelaerts, N., Macente, J., Smits, A., Annaert, P., Allegaert, K., (2023) Challenges Related to Acquisition of Physiological Data for Physiologically Based Pharmacokinetic (PBPK) Models in Postpartum, Lactating Women and Breastfed Infants—A Contribution from the ConcePTION Project. Pharmaceutics, 15(11):2618. https://doi.org/10.3390/pharmaceutics15112618