Placental transfer and tissue accumulation of dolutegravir in the ex vivo human cotyledon perfusion model.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
21
02
2019
accepted:
12
07
2019
entrez:
14
8
2019
pubmed:
14
8
2019
medline:
29
2
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31408460
doi: 10.1371/journal.pone.0220323
pii: PONE-D-19-05252
pmc: PMC6692001
doi:
Substances chimiques
HIV Integrase Inhibitors
0
Heterocyclic Compounds, 3-Ring
0
Oxazines
0
Piperazines
0
Pyridones
0
dolutegravir
DKO1W9H7M1
Antipyrine
T3CHA1B51H
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0220323Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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