The rise of opioid use disorder (OUD) among women of reproductive age is creating an urgent scientific and clinical challenge: how to provide effective treatment while protecting breastfeeding infants from unintended medication exposure. Researchers at Binghamton University, State University of New York, are launching a five-year, $3.3 million National Institutes of Health R01 project designed to answer one of the most persistent questions in maternal medicine—how medications used to treat OUD move from a mother’s bloodstream into breast milk, and what those drugs may do after they reach an infant.
The research team, led by Tao Zhang, associate professor and director of Binghamton’s Pharmacokinetics and Bioanalysis Facility, and Yanyan Li, assistant professor of pharmaceutical sciences, will combine laboratory experiments, clinical sampling and computational modeling. Their project, titled “Integrating A Novel Human Mammary Epithelium Assay with Mother-Infant PBPK-PD Modeling for Precision Dosing of OUD Medications in Lactating Mothers,” focuses on medication-assisted treatment, or MAT. The approach commonly involves buprenorphine, methadone or naltrexone, medicines that can reduce withdrawal symptoms, suppress cravings and lower the risk of overdose. Although MAT may be compatible with breastfeeding in some circumstances, detailed evidence about drug transfer and infant effects remains limited.
Breastfeeding women are frequently excluded from clinical trials because of ethical and safety concerns, leaving physicians with incomplete information when counseling patients who are receiving OUD treatment. The absence of reliable lactation data makes it difficult to determine how much medication enters breast milk, how concentrations change over time and whether exposure varies according to dosage, formulation or maternal metabolism. “There’s a knowledge gap,” Zhang said, explaining that mothers need clearer answers about whether medications are safe and how much of a drug may reach their milk. The new project is intended to replace broad assumptions with measurements and predictive tools that can support individualized medical decisions.
A central element of the study will be a new cell-based assay that recreates important features of the human mammary epithelium, the layer of cells responsible for regulating movement between maternal blood and breast milk. Rather than relying exclusively on direct sampling from mothers, researchers will use this experimental system to investigate how OUD medications cross mammary tissue and which biological properties influence that transfer. Drug concentration, molecular characteristics, protein binding and transport processes can all affect whether a compound accumulates in milk. A human mammary model could therefore provide a controlled way to examine mechanisms that are difficult to isolate in clinical studies.
The laboratory data will be integrated with samples collected from lactating mothers receiving MAT through clinical sites associated with Upstate Medical University. Nevena Radonjic, Cecilia Zemanek and Anastasia Sedykh are part of the Upstate clinical team, while Yuan Fang, an assistant professor at Old Dominion University, will contribute statistical expertise. Maternal and infant samples will be analyzed to determine medication concentrations and biological markers. The researchers plan to compare observed values with predictions generated by physiologically based pharmacokinetic, or PBPK, models, which represent drug absorption, distribution, metabolism and elimination across organs and tissues.
PBPK modeling can be especially valuable when clinical data are scarce. These models use information about physiology, drug chemistry, enzymes, transporters and dosing schedules to estimate how a medication behaves in a particular population. In this project, the models will be adapted to account for lactation and the linked biology of mother and infant. The team intends to predict drug levels across different formulations and treatment conditions, then test those predictions against real-world clinical measurements. A pharmacokinetic-pharmacodynamic, or PBPK-PD, framework could eventually connect exposure levels with potential biological effects, helping clinicians balance treatment benefits for the mother against possible risks to the infant.
Li’s research adds another dimension to the project by examining how early-life exposure may influence inflammation and the gut microbiome. Her work focuses on inflammatory diseases, gut biology and the relationship between the microbiome and the brain. Previous research from her group has suggested that interventions early in life can alter the gut microbiome more dramatically than interventions introduced later, potentially affecting vulnerability to inflammatory disease. In the new study, biomarkers measured in mothers and infants may help researchers investigate whether exposure to OUD medications is associated with changes in inflammatory pathways or microbial development. The project is exploratory in this area and is not designed to assume that medication exposure causes harm, but to identify biological signals that warrant closer study.
The collaboration brings together complementary expertise that is rarely available in a single research program. Zhang specializes in pharmacokinetic modeling and bioanalysis, while Li investigates inflammation, maternal influences and offspring health. The Upstate Medical University investigators will provide access to clinical populations and biological samples, and Fang will help analyze complex mother-infant data. Together, the researchers hope to establish a framework that can be applied not only to buprenorphine, methadone and naltrexone, but eventually to other medications used during lactation. The approach could also demonstrate how laboratory tissue models and computational simulations can reduce the need for ethically difficult or excessively large clinical studies.
The consequences of the work could extend beyond individual treatment decisions. Reliable data on drug transfer into breast milk may help regulatory agencies evaluate medications more accurately, guide the design of future clinical trials and support predictive mapping tools for lactating patients. For women with OUD, uncertainty itself can become a barrier to care: some may avoid treatment because they fear exposing their infants, while others may stop breastfeeding without access to clear, evidence-based guidance. By quantifying exposure and investigating possible infant responses, the Binghamton-led team hopes to support safer, more personalized treatment plans and reduce disparities affecting a population that has historically been underrepresented in drug research.
Zhang and Li also view the award as an opportunity to expand research capacity at Binghamton’s School of Pharmacy and Pharmaceutical Sciences, a relatively young program that has continued to build its academic and clinical profile. Their long-term goal is to generate enough evidence for physicians to provide more confident advice to breastfeeding patients undergoing OUD therapy. Over the next decade, the researchers hope their work will help transform lactation pharmacology from an area dominated by limited observations into one supported by integrated experiments, clinical measurements and predictive models. For mothers navigating opioid treatment while caring for an infant, that shift could mean more informed choices, fewer unnecessary disruptions to breastfeeding and a safer path through recovery.
Subject of Research: Opioid use disorder medications, breastfeeding, maternal and infant drug exposure, breast-milk drug transfer, pharmacokinetic modeling, inflammation and the gut microbiome.
Web References: Binghamton University School of Pharmacy and Pharmaceutical Sciences: https://www.binghamton.edu/pharmacy-and-pharmaceutical-sciences/ ; National Institutes of Health: https://www.nih.gov/
Image Credits: Binghamton University, State University of New York. Image of Yanyan Li: https://mediasvc.eurekalert.org/Api/v1/Multimedia/a30f4a0c-c404-4d7a-977e-9806855798e1/Rendition/low-res/Content/Public
Keywords: Opioid use disorder, opioids, breastfeeding, lactation, buprenorphine, methadone, naltrexone, medication-assisted treatment, breast milk, drug safety, pharmacokinetics, PBPK modeling, infant health, gut microbiome, inflammation, maternal health.
