Safety of medicines during breastfeeding – from case report to modeling: a contribution from the ConcePTION project

ABSTRACTIntroduction Despite many research efforts, current data on the safety of medicines during breastfeeding are either fragmented or lacking, resulting in restrictive labeling of most medicines. In the absence of pharmacoepidemiologic safety studies, risk estimation for breastfed infants is mainly derived from pharmacokinetic (PK) information on medicine. This manuscript provides a description and a comparison of the different methodological approaches that can yield reliable information on medicine transfer into human milk and the resulting infant exposure.Area Covered Currently, most information on medicine transfer in human milk relies on case reports or traditional PK studies, which generate data that can hardly be generalized to the population. Some methodological approaches, such as population PK (popPK) and physiologically based PK (PBPK) modeling, can be used to provide a more complete characterization of infant medicine exposure through human milk and simulate the most extreme situations while decreasing the burden of sampling in breastfeeding women.Expert opinion PBPK and popPK modeling are promising approaches to fill the gap in knowledge of medicine safety in breastfeeding, as illustrated with our escitalopram example.KEYWORDS: BreastfeedingBreastfed infantsDrug exposureHuman milkPharmacokineticsPhysiologically based pharmacokinetics Article highlights Infant exposure to medicines through human milk is an obvious driver for the assessment of medicine safety during breastfeeding.Population pharmacokinetic (popPK) and physiologically based pharmacokinetic (PBPK) modeling are two methodological approaches to assess medicine exposure in the infant through breastfeeding.The popPK approach provides an attractive sampling design for breastfeeding women who cannot be enrolled in traditional intensive sampling PK studies.The PBPK approach can predict the medicine pharmacokinetics at a very early stage of the pharmaceutical development, without human sampling.There is a need to further adapt popPK and PBPK approaches specifically for lactation studies.Declaration of interestMarie Teil is an employee of UCB Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Supplemental dataSupplemental data for this article can be accessed online at https://doi.org/10.1080/17425255.2023.2221847Additional informationFundingThis work has been completed as part of the ConcePTION study. The ConcePTION project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 821520. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and EFPIA. Nina Nauwelaerts also received a PhD scholarship by Research-Foundation-Flanders (1S50721N). The research project leading to these results was conducted as part of the ConcePTION consortium. This paper only reflects the personal views of the stated authors.