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Role of ABCB1, ABCG2, ABCC2 and ABCC5 transporters in placental passage of zidovudine
Author(s) -
Neumanova Zuzana,
Cerveny Lukas,
Ceckova Martina,
Staud Frantisek
Publication year - 2016
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.1993
Subject(s) - abcg2 , zidovudine , transplacental , atp binding cassette transporter , multidrug resistance associated protein 2 , pharmacology , transporter , p glycoprotein , multiple drug resistance , placenta , biology , virology , drug resistance , medicine , pregnancy , human immunodeficiency virus (hiv) , fetus , viral disease , biochemistry , genetics , gene
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. Copyright © 2016 John Wiley & Sons, Ltd.