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Placental transfer and tissue accumulation of dolutegravir in the ex vivo human cotyledon perfusion model.

Authors
  • Mandelbrot, Laurent1, 2, 3, 4
  • Ceccaldi, Pierre-François2, 3, 5
  • Duro, Dominique1, 6
  • Lê, Minh4, 7
  • Pencolé, Lucile1, 2, 4
  • Peytavin, Gilles4, 7
  • 1 Assistance Publique-Hôpitaux de Paris, Hôpital Louis Mourier, Service de Gynécologie-Obstétrique, Hôpitaux Universitaires Paris-Nord Val de Seine, Colombes, France. , (France)
  • 2 Université Paris-Diderot, Université Sorbonne Paris-Cité, Paris, France. , (France)
  • 3 Département Hospitalier Universitaire Risques et Grossesse, Paris, France. , (France)
  • 4 IAME, UMR 1137, INSERM, Paris, France. , (France)
  • 5 Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Service de Gynécologie-Obstétrique, Hôpitaux Universitaires Paris-Nord Val de Seine, Clichy, France. , (France)
  • 6 Agence Nationale de Recherches sur le Sida et Hépatites Virales (Inserm-ANRS), Paris, France. , (France)
  • 7 Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Pharmaco-Toxicology Department, Hôpitaux Universitaires Paris-Nord Val de Seine, Paris, France. , (France)
Type
Published Article
Journal
PLoS ONE
Publisher
Public Library of Science
Publication Date
Jan 01, 2019
Volume
14
Issue
8
Identifiers
DOI: 10.1371/journal.pone.0220323
PMID: 31408460
Source
Medline
Language
English
License
Unknown

Abstract

To determine the transplacental pharmacokinetics of the HIV integrase inhibitor dolutegravir. Maternal-to-fetal transfer across the term human placenta was investigated with the ex-vivo dually perfused cotyledon model, in 5 closed-circuit, recirculating experiments. Dolutegravir was added to a maternal perfusate containing antipyrine, a marker to validate the cotyledon's viability, and 2 g/liter of human albumin. After 3h of recirculating perfusion, the mean (± SD) DTG concentrations in the maternal and in the fetal compartments were respectively 2450 ± 286 ng/mL and 715 ± 369 ng/mL, with a fetal-to-maternal ratio of 34% ± 18% and a clearance index (in comparison with antipyrine transfer) of 79% ± 23%. The mean cotyledon accumulation index was 153% ± 25%. Fetal transplacental exposure to dolutegravir was considerable as well as accumulation in placental tissue. Whether this may lead to risks for the exposed fetus requires more investigation.

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