Interactions of protease inhibitors atazanavir and ritonavir with ABCB1, ABCG2, and ABCC2 transporters: Effect on transplacental disposition in rats

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F18%3A10382886" target="_blank" >RIV/00216208:11160/18:10382886 - isvavai.cz</a>
Result on the web
<a href="http://www.sciencedirect.com/science/article/pii/S0890623818300455" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0890623818300455</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.reprotox.2018.05.008" target="_blank" >10.1016/j.reprotox.2018.05.008</a>

Result language
angličtina
Original language name
Interactions of protease inhibitors atazanavir and ritonavir with ABCB1, ABCG2, and ABCC2 transporters: Effect on transplacental disposition in rats
Original language description
Atazanavir and ritonavir are preferred protease inhibitors frequently used in combination antiretroviral therapy for prevention of HIV mother-to-child transmission. Although their use is associated with higher risk of congenital anomalies, factors affecting atazanavir and ritonavir placental transfer are not known. This study is the first attempt to evaluate whether the placental drug efflux ATP-binding cassette (ABC) transporters, p-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), and/or multidrug resistance-associated proteins 2 (ABCC2), affect placental pharmacokinetics of atazanavir or ritonavir. Transport experiments across MDCKII cells expressing respective human ABC carrier showed that atazanavir is a substrate of ABCB1 and dual perfusion studies in a rat placenta confirmed this finding. In conclusion, we suggest that placental ABCB1 might reduce ATV maternal-to-fetal transfer and therefore represent a site for pharmacokinetic drug-drug interactions of ATV. Further studies in human placenta models are necessary to provide additional data closer to clinical environment.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy

Project
<a href="/en/project/GA17-16169S" target="_blank" >GA17-16169S: In vitro, in situ and ex vivo study of interactions of novel antiviral agents with drug transporters; effect on their passage across the placenta</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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