Role of ABCB1, ABCG2, ABCC2 and ABCC5 transporters in placental passage of zidovudine
Jazyk angličtina Země Velká Británie, Anglie Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26390406
DOI
10.1002/bdd.1993
Knihovny.cz E-zdroje
- Klíčová slova
- breast cancer resistance protein, multidrug resistance-associated protein 2, multidrug resistance-associated protein 5, p-glycoprotein, zidovudine,
- MeSH
- ABC transportéry antagonisté a inhibitory metabolismus MeSH
- akridiny farmakologie MeSH
- buňky MDCK MeSH
- indomethacin farmakologie MeSH
- lamivudin farmakologie MeSH
- látky proti HIV farmakokinetika MeSH
- lékové interakce MeSH
- placenta metabolismus MeSH
- potkani Wistar MeSH
- protein spojený s mnohočetnou rezistencí k lékům 2 MeSH
- psi MeSH
- techniky in vitro MeSH
- těhotenství MeSH
- tetrahydroisochinoliny farmakologie MeSH
- zidovudin farmakokinetika MeSH
- zvířata MeSH
- Check Tag
- psi MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ABC transportéry MeSH
- ABCC2 protein, human MeSH Prohlížeč
- akridiny MeSH
- Elacridar MeSH Prohlížeč
- indomethacin MeSH
- lamivudin MeSH
- látky proti HIV MeSH
- protein spojený s mnohočetnou rezistencí k lékům 2 MeSH
- tetrahydroisochinoliny MeSH
- zidovudin MeSH
Zidovudine (AZT) is one of the most frequently used antiretroviral drugs in prevention of perinatal transmission of HIV. However, safety concerns on AZT use in pregnancy still persist as severe side effects are associated with AZT exposure in children. In our study we aimed to contribute to current knowledge on AZT transplacental transport and to evaluate potential involvement of the main human drug efflux ATP-binding cassette (ABC) transporters, p-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2) and multidrug resistance-associated proteins 2 and 5 (ABCC2 and ABCC5) in the disposition of AZT between mother and fetus. In order to elucidate this issue we investigated the effect of selected ABC transporters on AZT transepithelial transport across MDCKII cell monolayers. In addition we used the in situ method of dually perfused rat term placenta to further study the role of ABC transporters in AZT transplacental transport. In vitro studies revealed significant effect of ABCB1 and ABCG2 on AZT transport which was subsequently confirmed also on organ level. Lamivudine, an antiretroviral agent commonly co-administered with AZT, did not affect ABC transporter-mediated AZT transfer.
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