Predicting Chemotherapy Distribution into Breast Milk for Breastfeeding Women Using a Population Pharmacokinetic Approach

David Damoiseaux, Daniel Centanni, Jos H Beijnen, Frédéric Amant, Alwin D R Huitema, Thomas P C Dorlo

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Abstract

BACKGROUND AND OBJECTIVE: Information on the distribution of chemotherapeutic drugs to breast milk is scarce, and reports are limited to small sample sizes. Anecdotal pharmacokinetic data have typically been acquired from lactating but non-breastfeeding patients who collect breast milk by means of an expression pump, which might not necessarily be representative for a breastfeeding population due to differences in milk production. Consequently, little is known about the variability of chemotherapy distribution to breast milk and the effect of milk production on the distribution of chemotherapy to breast milk. Our aim was to predict chemotherapy distribution to breast milk in a more realistic breastfeeding population and evaluate the effect of discarding breast milk on the potential chemotherapy exposure in infants.

METHODS: We developed a population pharmacokinetic model that described the breast milk production and the chemotherapy distribution to breast milk of a non-breastfeeding population, linked it to plasma pharmacokinetics, and extrapolated this to a breastfeeding population.

RESULTS: We found that cumulative relative infant doses (RID) were higher than 10% for cyclophosphamide and doxorubicin and approximately 1% for paclitaxel. Simulations allowed us to predict the cumulative RID and its variability in the population for patients with different milk productions and the amount of breast milk that has to be discarded to reach cumulative RIDs below 1%, 0.1%, and 0.01%. Discarding 1-2, 3-6, and 0-1 days of breast milk (depending on the milk production of the patient) resulted in cumulative RID below 1% for cyclophosphamide, doxorubicin, and paclitaxel, respectively.

CONCLUSION: Our results may help clinicians to derive the optimal breast milk discarding strategy for an individual patient that wants to breastfeed during chemotherapy and minimize chemotherapy exposure in their infants.

Original languageEnglish
Pages (from-to)969-980
Number of pages12
JournalClinical Pharmacokinetics
Volume62
Issue number7
DOIs
Publication statusPublished - Jul 2023

Keywords

  • Breast Feeding
  • Cyclophosphamide/metabolism
  • Doxorubicin
  • Female
  • Humans
  • Infant
  • Lactation
  • Milk, Human/metabolism
  • Paclitaxel

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