Model-Informed Evaluation of Hydroxyurea Exposure During Lactation

Area of Science:

• Pharmacokinetics
• Maternal-infant health
• Drug safety

Background:

• Hydroxyurea is a key therapy for sickle cell anemia.
• Limited data exists on hydroxyurea use during lactation.
• Assessing infant exposure is crucial for maternal treatment continuation.

Purpose of the Study:

• To develop a population pharmacokinetic (PK) model for hydroxyurea in maternal plasma and breast milk.
• To quantify infant exposure to hydroxyurea through breastfeeding.
• To evaluate the safety of maternal hydroxyurea therapy during lactation.

Main Methods:

• Population PK modeling using nonlinear mixed-effects modeling (HELPS study).
• Estimation of PK parameters for maternal plasma and breast milk.
• Stochastic simulations to calculate relative infant dose (RID) across infant ages 0-9 months.

Main Results:

• The PK model accurately described hydroxyurea disposition in plasma and breast milk.
• Simulations showed the estimated RID remained below the 10% safety threshold for all infant age groups.
• The model provides a quantitative framework for assessing lactational drug exposure.

Conclusions:

• Infant exposure to hydroxyurea via breastfeeding is unlikely to exceed the 10% safety threshold (WHO-recommended RID).
• This supports the continued use of hydroxyurea therapy in lactating mothers with sickle cell anemia.
• Clinical oversight is recommended for mothers using hydroxyurea while breastfeeding.