期刊
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
卷 73, 期 4, 页码 1013-1019出版社
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkx507
关键词
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资金
- Academy of Medical Sciences Starter Grant for Clinical Lecturers
- Wellcome Clinical Postdoctoral Training Fellowship [WT104422MA]
- Tertiary Education Trust Fund, Nigeria
- University of Liverpool, UK
- Wellcome Training Fellowship in Public Health and Tropical Medicine [204776/Z/16/Z]
- MRC [G0901364] Funding Source: UKRI
- Wellcome Trust [104422/Z/14/Z, 204776/Z/16/Z] Funding Source: Wellcome Trust
- Academy of Medical Sciences (AMS) [AMS-SGCL8-Waitt] Funding Source: researchfish
- Medical Research Council [G0901364] Funding Source: researchfish
- National Institute for Health Research [CL-2010-07-004] Funding Source: researchfish
- Wellcome Trust [104422/Z/14/Z] Funding Source: researchfish
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-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) 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.
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