Role of ABCB1, ABCG2, ABCC2 and ABCC5 transporters in placental passage of zidovudine
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26390406
DOI
10.1002/bdd.1993
Knihovny.cz E-resources
- Keywords
- breast cancer resistance protein, multidrug resistance-associated protein 2, multidrug resistance-associated protein 5, p-glycoprotein, zidovudine,
- MeSH
- ATP-Binding Cassette Transporters antagonists & inhibitors metabolism MeSH
- Acridines pharmacology MeSH
- Madin Darby Canine Kidney Cells MeSH
- Indomethacin pharmacology MeSH
- Lamivudine pharmacology MeSH
- Anti-HIV Agents pharmacokinetics MeSH
- Drug Interactions MeSH
- Placenta metabolism MeSH
- Rats, Wistar MeSH
- Multidrug Resistance-Associated Protein 2 MeSH
- Dogs MeSH
- In Vitro Techniques MeSH
- Pregnancy MeSH
- Tetrahydroisoquinolines pharmacology MeSH
- Zidovudine pharmacokinetics MeSH
- Animals MeSH
- Check Tag
- Dogs MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- ATP-Binding Cassette Transporters MeSH
- ABCC2 protein, human MeSH Browser
- Acridines MeSH
- Elacridar MeSH Browser
- Indomethacin MeSH
- Lamivudine MeSH
- Anti-HIV Agents MeSH
- Multidrug Resistance-Associated Protein 2 MeSH
- Tetrahydroisoquinolines MeSH
- Zidovudine 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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