Plasma and breast milk lumefantrine data in breastfeeding mothers with Uncomplicated plasmodium falciparum malaria

This file provides first clinical data on the transfer of lumefantrine from maternal plasma to breastmilk in women with uncomplicated plasmodium falciparum malaria treated with Artemether-Lumefantrine. Since 2001, Artemether-Lumefantrine has been the World Health Organisation's recomended treatment for uncomplicated plasmodium falciparum malaria. This combination is widely used in the general population including, breastfeeding women. Lumefantrine is highly lipid soluble, has a long half-life, and is expected to distribute widely in lipophilic compartments, such as breastmilk. Predictions of plasma-to-breastmilk transfer of lumefantrine, based on preclinical (rat) models and in silico Physiologically-Based Pharmacokinetic (PBPK) models, show inconsistent but generally high milk-to-plasma ratio (M:P>1.0). These predictions raise concern about the possibilty of toxic exposure of breastfeeding infants, or the risk of resistance development incase of infections at low concentratios. This observational clinical lactation pharmacokinetic study was undertaken in women diagnosed with uncomplicated plasmodium falciparum malaria. Here, we share results of an interim analysis from this study. From the six mothers included in the interim analysis, 78 plasma and 81 breastmilk samples were obtained. A wide inter-patient variability in lumefantrine concentration-time profiles was observed across different dose. Generally, both plasma and breastmilk concentrations increased across doses and plasma concentrations were consistently higher than breastmilk concentrations in paired plasma-breast milk samples, suggesting a milk-to-plasma ratio less than 1.0. Lumefantrine plasma and breastmilk concentrations were quantifiable upto 11 days after the last lumefantrine dose. These findings provide the first clinical evidence of lower and highly variable lumefantrine plasma-to-breast milk exposure, with the potential to support treatment recomendations and inform the refinement of lactation PBPK models.