Role of ABC and Solute Carrier Transporters in the Placental Transport of Lamivudine
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F16%3A10328397" target="_blank" >RIV/00216208:11160/16:10328397 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11150/16:10328397 RIV/00179906:_____/16:10328397
Result on the web
<a href="http://aac.asm.org/content/60/9/5563.full" target="_blank" >http://aac.asm.org/content/60/9/5563.full</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1128/AAC.00648-16" target="_blank" >10.1128/AAC.00648-16</a>
Alternative languages
Result language
angličtina
Original language name
Role of ABC and Solute Carrier Transporters in the Placental Transport of Lamivudine
Original language description
Lamivudine is one of the antiretroviral drugs of choice for the prevention of mother-to-child transmission (MTCT) in HIV-positive women. In this study, we investigated the relevance of drug efflux transporters P-glycoprotein (P-gp) (MDR1 [ABCB1]), BCRP (ABCG2), MRP2 (ABCC2), and MATE1 (SLC47A1) for the transmembrane transport and transplacental transfer of lamivudine. We employed in vitro accumulation and transport experiments on MDCK cells overexpressing drug efflux transporters, in situ-perfused rat term placenta, and vesicular uptake in microvillous plasma membrane (MVM) vesicles isolated from human term placenta. MATE1 significantly accelerated lamivudine transport in MATE1-expressing MDCK cells, whereas no transporter-driven efflux of lamivudine was observed in MDCK-MDR1, MDCK-MRP2, and MDCK-BCRP monolayers. MATE1-mediated efflux of lamivudine appeared to be a low-affinity process (apparent Km of 4.21 mM and Vmax of 5.18 nmol/mg protein/min in MDCK-MATE1 cells). Consistent with in vitro transport studies, the transplacental clearance of lamivudine was not affected by P-gp, BCRP, or MRP2. However, lamivudine transfer across dually perfused rat placenta and the uptake of lamivudine into human placental MVM vesicles revealed pH dependency, indicating possible involvement of MATE1 in the fetal-to-maternal efflux of the drug. To conclude, placental transport of lamivudine does not seem to be affected by P-gp, MRP2, or BCRP, but a pH-dependent mechanism mediates transport of lamivudine in the fetal-to-maternal direction. We suggest that MATE1 might be, at least partly, responsible for this transport.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FR - Pharmacology and apothecary chemistry
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Antimicrobial Agents and Chemotherapy
ISSN
0066-4804
e-ISSN
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Volume of the periodical
60
Issue of the periodical within the volume
9
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
5563-5572
UT code for WoS article
000389055400055
EID of the result in the Scopus database
2-s2.0-84983249402