Women often use medicines while breastfeeding, but we have very little information on how the mother’s medicines affect the breastfed infant. Researchers in the ConcePTION project have developed a generic work flow for predicting medicine concentrations in breast milk using physiologically-based pharmacokinetic (PBPK) modelling, just published in Pharmaceutics.
The prediction is done using computational model, an “in silico” tool that allows the assessment of drug exposure for a given dosing regimen. The team studied the performance of a generic physiologically-based pharmacokinetic (or PBPK) model to predict concentrations in human milk for ten medicines that are different on a physiochemical level. According to Nina Nauwelaerts and Julia Macente, PhD students at KU Leuven and lead authors, the medicines were selected because they have different elimination pathways, where they are taken care of by different enzymes involved in our metabolism, or the kidneys.
The team was able to predict the pharmacokinetic profile in breast milk, which means that we are able to predict how much of the medicine is present in the milk at different time points after the mother took the medicine, and how much of a substance crosses over to the mother’s millk. This makes it possible to estimate, or calculate, how much of the medicine the infant will receive through breastfeeding. Knowing more about the ‘pharmacokinetic behaviour’ in human milk will allows us to predict how much of a substance infants will be exposed to. The team managed to make this prediction for eight of the ten medicines: amoxicillin, cetirizine, caffeine, levetiracetam, metformin, sertraline, valproic acid and zidovudine.
For the other two drugs, nevirapine and tenofovir, the model overpredicted the concentration in milk. According to Nina Nauwelaerts, from a safety perspective, it is reassuring that the model never underpredicted the exposure to the medicine via breastfeeding.
“What is important to note is that the ‘dose’ that an infant could receive via breast milk that the model calculated were low for all medicines. Also when we compare that dose to what infants are prescribed when they need to be treated themselves”, says Nina Nauwelaerts.
The framework that this model has established here is an important step from where we are today. The PBPK models brings us closer to evidence-based safety assessments of the medicines that mothers receive, already in the early stages of drug development. Using this model makes it possible to develop quantitative information on how infants can be exposed to mothers’ medicines, before we are able to generate any clinical data.
Want to read the paper? It is published Open Access in Phramaeutics: Nauwelaerts N, Macente J, Deferm N, Bonan RH, Huang M-C, Van Neste M, Bibi D, Badee J, Martins FS, Smits A, Allegaert K, Bouillon T, Annaert P. Generic Workflow to Predict Medicine Concentrations in Human Milk Using Physiologically-Based Pharmacokinetic (PBPK) Modelling—A Contribution from the ConcePTION Project. Pharmaceutics. 2023; 15(5):1469. https://doi.org/10.3390/pharmaceutics15051469
By Josepine Fernow