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Role of ABC and Solute Carrier Transporters in the Placental Transport of Lamivudine

M. Ceckova, J. Reznicek, Z. Ptackova, L. Cerveny, F. Müller, M. Kacerovsky, MF. Fromm, JD. Glazier, F. Staud,

. 2016 ; 60 (9) : 5563-72. [pub] 20160822

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc17031593
E-zdroje Online Plný text

NLK Free Medical Journals od 1972 do Před 6 měsíci
Freely Accessible Science Journals od 1995 do Před 6 měsíci
PubMed Central od 1972 do Před 6 měsíci
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Open Access Digital Library od 1972-01-01
Open Access Digital Library od 1972-01-01

Odkazy

PubMed 27401571
DOI 10.1128/aac.00648-16
Knihovny.cz E-zdroje

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.

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