Investigation of a fully mechanistic physiologically based pharmacokinetics model of absorption to support predictions of milk concentrations in breastfeeding women and the exposure of infants: A case study for albendazole

Due to limited non-clinical and clinical data, European guidance recommends to discontinue breastfeeding when taking albendazole. The aim of this study was to consider the use of PBPK modeling to support the expected exposure in breastfed infants. A fully mechanistic PBPK approach was used to provide quantitative predictions of albendazole and its main active metabolite, albendazole sulfoxide, concentrations in plasma and breast milk of lactating women. The model predicted the exposure in adults and the large food effect, however, it does not predict all the clinical data for the exposure in children. Milk/plasma ratio predictions were also largely over-predicted for this lipophilic compound, but not for the less lipophilic metabolite. Predictions using the observed ratio and a worse-case exposure based on C_max predictions, suggest doses to children through milk will be low. However, more clinical data are required before full exposure predictions can be made to breastfed infants.