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• W2767583969 abstract "Objective: To determine the transplacental pharmacokinetics of the HIV integrase strand transfer inhibitor elvitegravir and of cobicistat, a cytochrome P450 inhibitor used as a pharmacoenhancer in antiretroviral therapy. Design and methods: Maternal-to-fetal transfer across the term human placenta was investigated with the ex-vivo dually perfused cotyledon model, in seven open-circuit experiments and 10 closed-circuit (recirculating) experiments. Elvitegravir and cobicistat were added to a maternal perfusate containing 2 g/l of human serum albumin and antipyrine, as a marker to validate the cotyledon's viability. Elvitegravir and cobicistat concentrations were measured using ultraperformance liquid chromatography coupled with tandem mass spectrometry. Results: For elvitegravir, in open-circuit experiments the mean (±SD) fetal transfer rate (FTR) (fetal/maternal concentration at steady state from 30 to 90 min) was 19 ± 13% and the mean clearance index was 0.46 ± 0.21; in the closed-circuit model, after 3 h of perfusion the FTR was 20 ± 10% and the mean accumulation index was 12.28 ± 5.57. For cobicistat, in the open perfusions the FTR was 23 ± 13% and the mean clearance index was 0.63 ± 0.34; in the closed perfusions after 3 h the fetal-to-maternal ratio of cobicistat was 21 ± 11%. The mean accumulation index was 3.46 ± 2.19 Conclusion: The two models concurred to show moderate placental transfer of elvitegravir and cobicistat across the placenta as well as elvitegravir accumulation in the placenta tissue. Whether this may lead to toxicities and modifications in fetal or placental metabolism requires clinical studies." @default.
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• W2767583969 date "2018-01-28" @default.
• W2767583969 modified "2023-10-16" @default.
• W2767583969 title "Placental transfer of elvitegravir and cobicistat in an ex-vivo human cotyledon double perfusion model" @default.
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• W2767583969 doi "https://doi.org/10.1097/qad.0000000000001681" @default.
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