PhD defence D. (Daphne) den Besten-Bertholee

Drugs in lactation: passage into breastmilk and infant exposure

Breastfeeding offers clear health benefits for both mother and child, and the WHO recommends exclusive breastfeeding for the first six months, continuing alongside solid foods up to two years. However, when mothers use medication, assessing safety becomes complex due to limited and sometimes conflicting data.

This thesis focuses on improving risk assessment for drug use during breastfeeding, particularly for antidepressants, antipsychotics, anti-epileptic drugs, and medications for inflammatory bowel disease. Key questions include whether drugs pass into breast milk and how much exposure occurs in infants. While the milk-to-plasma (M/P) ratio helps estimate drug transfer, it does not fully predict infant exposure, making direct infant measurements important.

To reduce burden on mothers and infants, innovative methods like dried blood spot (DBS) sampling were used, allowing home collection. Additionally, physiologically-based pharmacokinetic (PBPK) models combined existing data with knowledge of infant physiology to predict drug exposure.Studies showed that antidepressants such as sertraline, citalopram, and paroxetine are present in breast milk, but often result in undetectable drug levels in infants. This supports existing recommendations favoring sertraline and paroxetine during breastfeeding. In contrast, lamotrigine (used for epilepsy) does transfer to infants, highlighting the importance of therapeutic drug monitoring to keep maternal doses as low as effective.

A case study on mercaptopurine showed no detectable drug in breast milk four hours after intake, illustrating the value of tailored analysis by clinical pharmacists.Overall, combining clinical data, drug measurements, and modeling improves decision-making about safe medication use during breastfeeding.

Supervisor: D.J. (Daan) Touw
Co-supervisors: dr. P. (Paola) Mian, dr. P.G.J. ter Horst