A tutorial on physiologically based pharmacokinetic approaches in lactation research

Abstract

Abstract In breastfeeding mothers, managing medical conditions presents unique challenges, particularly concerning medication use and breastfeeding practices. The transfer of drugs into breast milk and subsequent exposure to nursing infants raises important considerations for drug safety and efficacy. Modeling approaches are increasingly employed to predict infant exposure levels, crucial for assessing drug safety during breastfeeding. Physiologically‐based pharmacokinetic (PBPK) modeling provides a valuable tool for predicting drug exposure in lactating individuals and their infants. This tutorial offers an overview of PBPK modeling in lactation research, covering key concepts, prediction approaches, and best practices for model development and application. We delve into milk composition dynamics and its influence on drug transfer into breast milk, addressing modeling considerations, knowledge gaps, and future research directions. Practical examples and case studies illustrate PBPK modeling application in lactation studies. We demonstrate how prediction algorithms for Milk‐to‐Plasma (M/P) ratios within a PBPK framework can support scenarios lacking clinical lactation data or extend the utility of available lactation clinical data to support further untested clinical scenarios. This tutorial aims to assist researchers and clinicians in understanding and applying PBPK modeling to understand and support clinical scenarios in breastfeeding mothers. Advances in PBPK modeling techniques, along with ongoing research on lactation physiology and drug disposition, promise further insights into drug transfer during lactation.