Role of nucleoside transporters in transplacental pharmacokinetics of nucleoside reverse transcriptase inhibitors zidovudine and emtricitabine

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F17%3A10365397" target="_blank" >RIV/00216208:11160/17:10365397 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S0143400417311657" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0143400417311657</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.placenta.2017.10.011" target="_blank" >10.1016/j.placenta.2017.10.011</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Role of nucleoside transporters in transplacental pharmacokinetics of nucleoside reverse transcriptase inhibitors zidovudine and emtricitabine

Popis výsledku v původním jazyce

Zidovudine (AZT) and emtricitabine (FTC) are effective and well tolerated antiretroviral drugs, routinely used in the prevention of perinatal HIV transmission. However, precise mechanism(s) involved in their transfer from mother to fetus are not fully elucidated. Since both drugs are nucleoside analogues, we hypothesized that the mechanisms of their transplacental passage might include quilibrative nucleoside transporters, ENT1 and/or ENT2. To address this issue, we performed in vitro accumulation assays in the BeWo placental trophoblast cell line, ex vivo uptake studies in fresh villous fragments isolated from human placenta and in situ dually perfused rat term placenta experiments. Applying this complex array of methods, we did not prove that ENTs play a significant role in transfer of AZT or FTC across the placenta. We conclude that the transplacental passage of AZT and FTC is independent of ENTs. Disposition of either compound into the fetal circulation should thus not be affected by ENT-mediated drug-drug interactions or placental expression of the transporters.

Název v anglickém jazyce

Role of nucleoside transporters in transplacental pharmacokinetics of nucleoside reverse transcriptase inhibitors zidovudine and emtricitabine

Popis výsledku anglicky

Zidovudine (AZT) and emtricitabine (FTC) are effective and well tolerated antiretroviral drugs, routinely used in the prevention of perinatal HIV transmission. However, precise mechanism(s) involved in their transfer from mother to fetus are not fully elucidated. Since both drugs are nucleoside analogues, we hypothesized that the mechanisms of their transplacental passage might include quilibrative nucleoside transporters, ENT1 and/or ENT2. To address this issue, we performed in vitro accumulation assays in the BeWo placental trophoblast cell line, ex vivo uptake studies in fresh villous fragments isolated from human placenta and in situ dually perfused rat term placenta experiments. Applying this complex array of methods, we did not prove that ENTs play a significant role in transfer of AZT or FTC across the placenta. We conclude that the transplacental passage of AZT and FTC is independent of ENTs. Disposition of either compound into the fetal circulation should thus not be affected by ENT-mediated drug-drug interactions or placental expression of the transporters.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/GA17-16169S" target="_blank" >GA17-16169S: In vitro, in situ a ex vivo studium interakcí nových antivirotik s lékovými transportéry; vliv na jejich přestup přes placentu</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Placenta

ISSN

0143-4004

e-ISSN

—

Svazek periodika

60

Číslo periodika v rámci svazku

December

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

7

Strana od-do

86-92

Kód UT WoS článku

000417981200012

EID výsledku v databázi Scopus

2-s2.0-85033443395