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Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother–infant pairs
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 pharmaco...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890695/ https://www.ncbi.nlm.nih.gov/pubmed/29309634 http://dx.doi.org/10.1093/jac/dkx507 |
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author | Waitt, Catriona Olagunju, Adeniyi Nakalema, Shadia Kyohaire, Isabella Owen, Andrew Lamorde, Mohammed Khoo, Saye |
author_facet | Waitt, Catriona Olagunju, Adeniyi Nakalema, Shadia Kyohaire, Isabella Owen, Andrew Lamorde, Mohammed Khoo, Saye |
author_sort | Waitt, Catriona |
collection | PubMed |
description | 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 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. |
format | Online Article Text |
id | pubmed-5890695 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-58906952018-04-13 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 Olagunju, Adeniyi Nakalema, Shadia Kyohaire, Isabella Owen, Andrew Lamorde, Mohammed Khoo, Saye J Antimicrob Chemother Original Research 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 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. Oxford University Press 2018-04 2018-01-04 /pmc/articles/PMC5890695/ /pubmed/29309634 http://dx.doi.org/10.1093/jac/dkx507 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Waitt, Catriona Olagunju, Adeniyi Nakalema, Shadia Kyohaire, Isabella Owen, Andrew Lamorde, Mohammed Khoo, Saye Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother–infant pairs |
title | Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother–infant pairs |
title_full | Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother–infant pairs |
title_fullStr | Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother–infant pairs |
title_full_unstemmed | Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother–infant pairs |
title_short | Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother–infant pairs |
title_sort | plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing african mother–infant pairs |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890695/ https://www.ncbi.nlm.nih.gov/pubmed/29309634 http://dx.doi.org/10.1093/jac/dkx507 |
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