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- Title
Placental transfer and tissue accumulation of dolutegravir in the ex vivo human cotyledon perfusion model.
- Authors
Mandelbrot, Laurent; Ceccaldi, Pierre-François; Duro, Dominique; Lê, Minh; Pencolé, Lucile; Peytavin, Gilles
- Abstract
Objective: To determine the transplacental pharmacokinetics of the HIV integrase inhibitor dolutegravir. Study design: 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. Results: 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%. Conclusion: 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.
- Subjects
HIV integrase inhibitors; COTYLEDONS; PERFUSION; DEVELOPMENTAL biology
- Publication
PLoS ONE, 2019, Vol 14, Issue 8, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0220323