PI-076 - CANNABIDIOL EXPOSURES IN BREASTFED INFANTS COMPARED TO CHILDREN AS PREDICTED BY PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELING.

C. Yeung¹, K. Bertrand², B. Best², E. Capparelli², C. Chambers², S. Ito³, J. Momper², A. Edginton¹; ¹University of Waterloo, Waterloo, Ontario, Canada, ²University of California, San Diego, La Jolla, CA, USA, ³Hospital for Sick Children, Toronto, Ontario, Canada.

Background: Current guidance is to avoid cannabidiol (CBD) and CBD-containing products when breastfeeding due to potential risks to the infant. Yet, limited data are available on breastfed infant CBD exposures with mothers taking cannabis products. We predicted the range of breastfed infant CBD exposures during real world maternal cannabis use.

Methods: We scaled a prior adult CBD physiologically based pharmacokinetic (PBPK) model to infants. Growth and maturation, and variability around anatomy and physiology were accounted for to give a realistic infant population. The model was evaluated in published data from 4-11 year old children receiving CBD orally (5-20 mg/kg/day).3 Infant doses were simulated with milk intake volumes4 and milk CBD concentrations (human milk biorepository5, 297 samples). We simulated daily steady state AUC for breastfed infants and children given the doses via milk and therapeutic dose directly, respectively.

Results: The PBPK model accurately predicted CBD AUC0-t in children. Milk CBD concentrations were described by a frequency distribution with a geometric mean of 0.56 ng/mL (standard deviation 5.5). The Figure shows the predicted daily steady state AUC of children and breastfed infants.

Conclusion: In comparison to children, our results suggest minimal infant exposure of CBD through breastfeeding during real world maternal cannabis use.

1. Devinsky, O. et al. Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology. 90, e1204-e1211 (2018).
2. Yeung, C. H. T., Fong, S., Malik, P. R. V., Edginton, A. N. Quantifying breast milk intake by term and preterm infants for input into paediatric physiologically based pharmacokinetic models. Matern. Child. Nutr. 16, e12938 (2020).
3. Bertrand, K. A., Hanan, N. J., Honerkamp-Smith, G., Best, B. M., Chambers, C. D. Marijuana use by breastfeeding mothers and cannabinoid concentrations in breast milk. Pediatrics. 142(3), e20181076 (2018).

Figure. CBD PBPK model predicted daily steady state AUC of children (N = 100, receiving 5 mg/kg/day) compared to breastfed infants across age groups (N = 100 per group, receiving CBD in milk doses).