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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Plasma and intracellular tenofovir pharmacokinetics in the neonate (ANRS 12109 trial, step 2)
Antimicrobial Agents and Chemotherapy, Volume 55, No. 6, Year 2011
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Description
The objective of this study was to investigate for the first time tenofovir (TFV) pharmacokinetics in plasma and peripheral blood mononuclear cells (PBMCs) of the neonate. HIV-1-infected pregnant women received two tablets of tenofovir disoproxil fumarate (TDF; 300 mg) and emtricitabine (FTC; 200 mg) at onset of labor and then one tablet daily for 7 days postpartum. A single dose of 13 mg/kg of body weight of TDF was administered to 36 neonates within 12 h of life after the HIV-1-infected mothers had been administered two tablets of TDF-emtricitabine at delivery. A total of 626 samples collected within the 2 days after the drug administration were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and analyzed by a population approach. In the neonate, the median TFV plasma area under the curve and minimal and maximal concentrations, respectively, were 3.73 mg/liter · h and 0.076 and 0.29 mg/liter. In PBMCs, TFV concentrations were detectable in all fetuses, whereas tenofovir diphosphate (TFV-DP) was quantifiable in only two fetuses, suggesting a lag in appearance of TFV-DP. The median TFV-DP neonatal concentration was 146 fmol/10 6 cells (interquartile range [IQR], 53 to 430 fmol/10 6 cells); two neonates had very high TFV-DP concentrations (1,530 and 2963 fmol/10 6 cells). The 13-mg/kg TDF dose given to neonates produced plasma TFV and intracellular active TFV-DP concentrations similar to those in adults. This dose should be given immediately after birth to reduce the delay before the active compound TFV-DP appears in cells. Copyright © 2011, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Hirt, Déborah
France, Paris
Hopital Cochin Ap-hp
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Paris
Inserm
Ékouévi, Didier Koumavi
Cote D'ivoire, Abidjan
Programme Pac-ci
France, Paris
Inserm
Pruvost, A. G.
France, Gif-sur-yvette
Institut de Biologie et de Technologies de Saclay
Urien, Saík
France, Paris
Hopital Cochin Ap-hp
France, Paris
Inserm
France, Paris
Université Paris Cité
Arrivé, Élise
France, Paris
Inserm
Blanche, Stéphane
France, Paris
Hôpital Necker Enfants Malades
Avit, Divine
Cote D'ivoire, Abidjan
Programme Pac-ci
Amani-Bossé, Clarisse
Cote D'ivoire, Abidjan
Programme Pac-ci
Nyati, Mandisa M.
South Africa, Johannesburg
University of the Witwatersrand
Legote, Shini
South Africa, Johannesburg
University of the Witwatersrand
Ek, Meng L.
Cambodia, Phnom Penh
Hopital Calmette
Say, Leakhena
Cambodia, Phnom Penh
Institut Pasteur du Cambodge
McIntyre, James Alasdair
South Africa, Johannesburg
University of the Witwatersrand
Dabis, Franćois Ç.Ois
France, Paris
Inserm
Tréluyer, Jean Marc
France, Paris
Hopital Cochin Ap-hp
France, Paris
Inserm
France, Paris
Université Paris Cité
Statistics
Citations: 42
Authors: 15
Affiliations: 10
Identifiers
Doi:
10.1128/AAC.01377-10
ISSN:
00664804
e-ISSN:
10986596
Research Areas
Infectious Diseases
Maternal And Child Health
Study Design
Cross Sectional Study
Participants Gender
Female