Are active efflux transporters contributing to infant drug exposure via breastmilk? A longitudinal study

Although most drugs are considered safe and compatible with breastfeeding, cases of toxic drug exposure have been reported. Active efflux transporters have been implicated as a mechanism in the transfer of drugs from mother to baby via breastmilk. Using breastmilk as a source of human mammary epithelial cells, this novel longitudinal study investigated the expression of four active transporters, namely, MDR1, MRP1, MRP2 and BCRP in the lactating human breast. BCRP gene was found to be strongly overexpressed with levels peaking at 5 months postpartum, potentially indicating a time where a breastfed infant may be at risk of inadvertent exposure to BCRP substrates. Serum albumin, a major component of human breastmilk was increasingly downregulated as lactation progresses. Xanthine oxidase/dehydrogenase, an enzyme in breastmilk attributed to a reduced risk of gastroenteritis caused by Escherichia coli and Salmonella enteritides, was downregulated. Lysozyme and fatty acid synthase are progressively upregulated. This study also shows that breastmilk-derived epithelial cells, when propagated in culture, exhibit characteristics significantly different to those derived directly from breastmilk. This serves to warn that in vitro studies are not a true representation of in vivo processes in the lactating breast; hence, application of in vitro data should be conducted with caution.