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

• Published in: Journal of antimicrobial chemotherapy 2018-04, Vol.73 (4), p.1013-1019
• Main Authors: Waitt, Catriona, Olagunju, Adeniyi, Nakalema, Shadia, Kyohaire, Isabella, Owen, Andrew, Lamorde, Mohammed, Khoo, Saye
• Format: Article
• Language: English
• Subjects: Adult; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - pharmacokinetics; Breast Feeding; Chromatography, Liquid; Cohort Studies; Emtricitabine - administration & dosage; Emtricitabine - pharmacokinetics; Female; Humans; Infant; Lamivudine - administration & dosage; Lamivudine - pharmacokinetics; Milk, Human - chemistry; Mothers; Nigeria; Original Research; Plasma - chemistry; Tandem Mass Spectrometry; Tenofovir - administration & dosage; Tenofovir - pharmacokinetics; Uganda; Young Adult
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkx507

Breast milk transfer of first-line ART from mother to infant is not fully understood. To determine the concentrations of lamivudine, emtricitabine and tenofovir in maternal blood, breast milk and infant blood from breastfeeding mother-infant pairs. 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 was conducted. 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 using LC-MS/MS, with non-compartmental analysis to calculate key pharmacokinetic parameters. Peak concentrations in breast milk from women taking lamivudine and emtricitabine occurred later than in plasma (4-8 h compared with 2 h for lamivudine and 2-4 h for emtricitabine). Consequently, the milk-to-plasma (M:P) ratio of lamivudine taken once daily was 0.95 (0.82-1.15) for AUC0-12, whereas for AUC12-20 this was 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 200 mg of emtricitabine once daily, the median M:P ratio was 3.01 (2.06-3.38). Three infants (19%) had measurable emtricitabine [median 18.5 (17.6-20.8) ng/mL]. For 300 mg of tenofovir once daily, the median M:P ratio was 0.015 (0-0.03) and no infant had measurable tenofovir concentrations. Emtricitabine and lamivudine accumulate in breast milk and were detected in breastfeeding infants. In contrast, tenofovir penetrates the breast milk to a small degree, but is undetectable in breastfeeding infants.