Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother-infant pairs

Abstract

Background: Breast milk transfer of first-line ART from mother to infant is not fully understood.Objectives: To determine the concentrations of lamivudine, emtricitabine and tenofovir in maternal blood,breast milk and infant blood from breastfeeding mother-infant pairs.Methods: Intensive pharmacokinetic sampling of maternal dried blood spots (DBS), dried breast milk spots(DBMS) and infant DBS from 30 Ugandan and 29 Nigerian mothers receiving first-line ART and their infants wasconducted. DBS and DBMS were collected pre-dose and at 5-6 timepoints up to 12 h following observed dosing.Infant DBS were sampled twice during this period. Lamivudine, emtricitabine and tenofovir were quantified usingLC-MS/MS, with non-compartmental analysis to calculate key pharmacokinetic parameters.Results: Peak concentrations in breast milk from women taking lamivudine and emtricitabine occurred laterthan in plasma (4-8 h compared with 2 h for lamivudine and 2-4 h for emtricitabine). Consequently, the milk-toplasma(M:P) ratio of lamivudine taken once daily was 0.95 (0.82-1.15) for AUC 0-12 , whereas for AUC 12-20 thiswas 3.04 (2.87-4.16). Lamivudine was detectable in 36% (14/39) of infants [median 17.7 (16.3-22.7) ng/mL].For 200mg of emtricitabine once daily, the median M:P ratio was 3.01 (2.06-3.38). Three infants (19%) hadmeasurable emtricitabine [median 18.5 (17.6-20.8) ng/mL]. For 300mg of tenofovir once daily, the median M:Pratio was 0.015 (0-0.03) and no infant had measurable tenofovir concentrations.Conclusions: Emtricitabine and lamivudine accumulate in breast milk and were detected in breastfeedinginfants. In contrast, tenofovir penetrates the breast milk to a small degree, but is undetectable in breastfeedinginfants.