Plasma and Breast Milk Pharmacokinetics of Emtricitabine, Tenofovir and Lamivudine Using Dried Blood and Breast Milk Spots in Nursing African Mother-Infant Pairs

Waitt, Catriona ORCID: 0000-0003-0134-5855, Olagunju, Adeniyi ORCID: 0000-0002-6588-5749, Nakalema, Shadia, Kyohaire, Isabella, Owen, Andrew ORCID: 0000-0002-9819-7651, Lamorde, Mohammed and Khoo, Saye ORCID: 0000-0002-2769-0967 (2018) Plasma and Breast Milk Pharmacokinetics of Emtricitabine, Tenofovir and Lamivudine Using Dried Blood and Breast Milk Spots in Nursing African Mother-Infant Pairs. Journal of Antimicrobial Chemotherapy, 73 (4). pp. 1013-1019.

Text Plasma and breast milk pharmacokinetics of emtricitabine tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother infant pairs Accepted version.docx - Author Accepted Manuscript Download (318kB)

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 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. Results: 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. Conclusions: 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.

Item Type:	Article
Uncontrolled Keywords:	Milk, Human, Plasma, Humans, Lamivudine, Anti-HIV Agents, Chromatography, Liquid, Cohort Studies, Mothers, Breast Feeding, Adult, Infant, Uganda, Nigeria, Female, Male, Tandem Mass Spectrometry, Young Adult, Tenofovir, Emtricitabine
Depositing User:	Symplectic Admin
Date Deposited:	08 Jan 2018 07:39
Last Modified:	19 Jan 2023 06:46
DOI:	10.1093/jac/dkx507
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3015522