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Placental transfer and tissue accumulation of dolutegravir in the ex vivo human cotyledon perfusion model.
- Source :
-
PloS one [PLoS One] 2019 Aug 13; Vol. 14 (8), pp. e0220323. Date of Electronic Publication: 2019 Aug 13 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- Objective: To determine the transplacental pharmacokinetics of the HIV integrase inhibitor dolutegravir.<br />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.<br />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%.<br />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.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Antipyrine pharmacokinetics
Female
HIV Integrase Inhibitors analysis
Heterocyclic Compounds, 3-Ring analysis
Humans
Models, Biological
Oxazines
Perfusion
Piperazines
Placenta chemistry
Pregnancy
Pyridones
HIV Integrase Inhibitors pharmacokinetics
Heterocyclic Compounds, 3-Ring pharmacokinetics
Maternal-Fetal Exchange
Placenta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 14
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 31408460
- Full Text :
- https://doi.org/10.1371/journal.pone.0220323