title: Plasma and intracellular tenofovir pharmacokinetics in the neonate (ANRS 12109 trial, step 2).
abstract: 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/10⁶ cells (interquartile range [IQR], 53 to 430 fmol/10⁶ cells); two neonates had very high TFV-DP concentrations (1,530 and 2963 fmol/10⁶ 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.
authors.affiliation: Unité de Recherche Clinique, Hôpital Tarnier, 89 Rue d'Assas, 75006 Paris, France. deborah.hirt@univ-paris5.fr
authors.forename: Déborah
authors.initials: D
authors.lastname: Hirt
authors.forename: Didier K
authors.initials: DK
authors.lastname: Ekouévi
authors.forename: Alain
authors.initials: A
authors.lastname: Pruvost
authors.forename: Saïk
authors.initials: S
authors.lastname: Urien
authors.forename: Elise
authors.initials: E
authors.lastname: Arrivé
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Divine
authors.initials: D
authors.lastname: Avit
authors.forename: Clarisse
authors.initials: C
authors.lastname: Amani-Bosse
authors.forename: Mandisa
authors.initials: M
authors.lastname: Nyati
authors.forename: Shini
authors.initials: S
authors.lastname: Legote
authors.forename: Meng L
authors.initials: ML
authors.lastname: Ek
authors.forename: Leakhena
authors.initials: L
authors.lastname: Say
authors.forename: James
authors.initials: J
authors.lastname: McIntyre
authors.forename: François
authors.initials: F
authors.lastname: Dabis
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Tréluyer
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000225:Adenine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D005260:Female; D015497:HIV-1; D006801:Humans; D007231:Infant, Newborn / Q000378:metabolism*; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D063065:Organophosphonates / Q000493:pharmacokinetics*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine