Assistance Publique-Hôpitaux de Paris, Hôpital Louis Mourier, Service de Gynécologie-Obstétrique, Hôpitaux Universitaires Paris-Nord Val de Seine, Colombes, France.
Université Paris-Diderot, Université Sorbonne Paris-Cité, Paris, France.
PLoS One. 2019 Aug 13;14(8):e0220323. doi: 10.1371/journal.pone.0220323. eCollection 2019.
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.
研究人类胎盘中 HIV 整合酶抑制剂多替拉韦的跨胎盘药代动力学。
采用离体双灌流绒毛模型，在 5 个闭路、再循环实验中研究了足月时母体到胎儿的转移。多替拉韦被添加到含有安替比林（一种验证绒毛膜活力的标志物）和 2 g/L 人白蛋白的母体灌流液中。
再循环灌注 3 小时后，母、胎儿腔室中多替拉韦的平均（±SD）浓度分别为 2450 ± 286ng/ml 和 715 ± 369ng/ml，胎儿与母体的比值为 34% ± 18%，清除指数（与安替比林转移相比）为 79% ± 23%。平均胎盘组织蓄积指数为 153% ± 25%。
胎儿通过胎盘暴露于多替拉韦的程度以及在胎盘组织中的蓄积量都相当可观。这是否会给暴露的胎儿带来风险，还需要进一步研究。
