Etravirine inhibits ABCG2 drug transporter and affects transplacental passage of tenofovir disoproxil fumarate

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F16%3A10328394" target="_blank" >RIV/00216208:11160/16:10328394 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S0143400416305380" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0143400416305380</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.placenta.2016.09.019" target="_blank" >10.1016/j.placenta.2016.09.019</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Etravirine inhibits ABCG2 drug transporter and affects transplacental passage of tenofovir disoproxil fumarate

Popis výsledku v původním jazyce

All HIV positive pregnant women should receive combination antiretroviral therapy (cART) to prevent mother-to-child transmission (MTCT) of the virus. It has recently been shown that fetal exposure of nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF) and abacavir is decreased by placental ABC transporters p-glycoprotein (ABCB1) and BCRP (ABCG2). The aim of this study was to evaluate transporter-mediated drug-drug interactions (DDI) between etravirine (TMC125), a novel non-nucleoside reverse transcriptase inhibitor used in cART, and the NRTIs and to assess the relevance of such DDI for transplacental pharmacokinetics of TDF and abacavir. We confirmed significant inhibition of ABCG2 but not ABCB1 by etravirine in hoechst accumulation assays. In transport studies on MDCKII-ABCG2 monolayers etravirine completely abolished the ABCG2-mediated transfer of [3H]-TDF. Similar effect was observed in [3H]-abacavir albeit at markedly lower etravirine concentration. Using dually perfused rat placenta, etravirine co-administration resulted in reduced fetal-to-maternal passage of TDF but not abacavir.

Název v anglickém jazyce

Etravirine inhibits ABCG2 drug transporter and affects transplacental passage of tenofovir disoproxil fumarate

Popis výsledku anglicky

All HIV positive pregnant women should receive combination antiretroviral therapy (cART) to prevent mother-to-child transmission (MTCT) of the virus. It has recently been shown that fetal exposure of nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF) and abacavir is decreased by placental ABC transporters p-glycoprotein (ABCB1) and BCRP (ABCG2). The aim of this study was to evaluate transporter-mediated drug-drug interactions (DDI) between etravirine (TMC125), a novel non-nucleoside reverse transcriptase inhibitor used in cART, and the NRTIs and to assess the relevance of such DDI for transplacental pharmacokinetics of TDF and abacavir. We confirmed significant inhibition of ABCG2 but not ABCB1 by etravirine in hoechst accumulation assays. In transport studies on MDCKII-ABCG2 monolayers etravirine completely abolished the ABCG2-mediated transfer of [3H]-TDF. Similar effect was observed in [3H]-abacavir albeit at markedly lower etravirine concentration. Using dually perfused rat placenta, etravirine co-administration resulted in reduced fetal-to-maternal passage of TDF but not abacavir.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

—

Projekt

<a href="/cs/project/GP13-31118P" target="_blank" >GP13-31118P: Interakce antiretrovirálních léčiv s lidskými lékovými transportéry in vitro s ohledem na transplacentární farmakokinetiku</a><br>

Návaznosti

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

Rok uplatnění

2016

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

47

Číslo periodika v rámci svazku

November

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

6

Strana od-do

124-129

Kód UT WoS článku

000387525800017

EID výsledku v databázi Scopus

2-s2.0-84991220909