Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother-infant pairs.
J Antimicrob Chemother
; 73(4): 1013-1019, 2018 04 01.
Article
em En
| MEDLINE
| ID: mdl-29309634
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 (MP) 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 MP 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 MP 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Plasma
/
Aleitamento Materno
/
Lamivudina
/
Fármacos Anti-HIV
/
Tenofovir
/
Emtricitabina
/
Leite Humano
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Infant
/
Male
País como assunto:
Africa
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article