Effect of drug efflux transporters on placental transport of antiretroviral agent abacavir
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26169552
DOI
10.1016/j.reprotox.2015.07.070
PII: S0890-6238(15)30001-0
Knihovny.cz E-zdroje
- Klíčová slova
- Abacavir, Breast cancer resistance protein, HIV, Multidrug resistance-associated proteins, P-glycoprotein, Transplacental pharmacokinetics,
- MeSH
- antiretrovirové látky farmakokinetika MeSH
- buňky MDCK MeSH
- dideoxynukleosidy farmakokinetika MeSH
- lidé MeSH
- placenta metabolismus MeSH
- potkani Wistar MeSH
- protein spojený s mnohočetnou rezistencí k lékům 2 MeSH
- proteiny spojené s mnohočetnou rezistencí k lékům metabolismus MeSH
- psi MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- psi MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- abacavir MeSH Prohlížeč
- ABCC2 protein, human MeSH Prohlížeč
- antiretrovirové látky MeSH
- dideoxynukleosidy MeSH
- protein spojený s mnohočetnou rezistencí k lékům 2 MeSH
- proteiny spojené s mnohočetnou rezistencí k lékům MeSH
Abacavir is as a frequent part of combination antiretroviral therapy used in pregnant women. The aim of this study was to investigate, using in vitro, in situ and ex vivo experimental approaches, whether the transplacental pharmacokinetics of abacavir is affected by ATP-binding cassette (ABC) efflux transporters functionally expressed in the placenta: P-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), multidrug resistance-associated protein 2 (ABCC2) and multidrug resistance-associated protein 5 (ABCC5). In vitro transport assays revealed that abacavir is a substrate of human ABCB1 and ABCG2 transporters but not of ABCC2 or ABCC5. In addition, in situ experiments using dually perfused rat term placenta confirmed interactions of abacavir with placental Abcb1/Abcg2. In contrast, uptake studies in human placental villous fragments did not reveal any interaction of abacavir with efflux transporters suggesting a large contribution of passive diffusion and/or influx mechanisms to net transplacental abacavir transfer.
Citace poskytuje Crossref.org
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