Long-term administration of tenofovir or emtricitabine to pregnant rats; effect on Abcb1a, Abcb1b and Abcg2 expression in the placenta and in maternal and fetal organs

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F16%3A10328389" target="_blank" >RIV/00216208:11160/16:10328389 - isvavai.cz</a>

Výsledek na webu

<a href="http://onlinelibrary.wiley.com/doi/10.1111/jphp.12495/full" target="_blank" >http://onlinelibrary.wiley.com/doi/10.1111/jphp.12495/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/jphp.12495" target="_blank" >10.1111/jphp.12495</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Long-term administration of tenofovir or emtricitabine to pregnant rats; effect on Abcb1a, Abcb1b and Abcg2 expression in the placenta and in maternal and fetal organs

Popis výsledku v původním jazyce

Objectives Tenofovir and emtricitabine are very effective and well-tolerated antiretrovirals representing current backbone of the antiretroviral combination regimens for the prevention of perinatal HIV transmission. The aim of our study was to determine whether tenofovir or emtricitabine administered in long-term fashion affect expression of two widely described pharmacokinetic determinants, P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), in maternal or fetal biological tissues. Methods For this purpose, pregnant Wistar rats were administered tenofovir (2.25 mg/kg/day), emtricitabine (3.5 mg/kg/day) or saline i.m. for 10 days (from the 12th to 21st gestation day). On the 22nd day, the placenta and maternal/fetal intestine, brain, kidneys and liver were sampled and analysed for Abcb1a, Abcb1b and Abcg2 expression; placental and newborns' weights were also monitored. Key findings We found that long-term application of tenofovir or emtricitabine did not significantly affect expression of Abcb1a, Abcb1b and Abcg2 in either maternal or fetal organs. However, tenofovir administration significantly increased placenta-to-birthweight ratio, a strong indicator of various diseases occurring later in life. Conclusions Our data broaden current knowledge on safety profile of tenofovir and emtricitabine use in pregnancy. Nevertheless, further research in other mammal species, including humans, is important to fully elucidate this issue.

Název v anglickém jazyce

Long-term administration of tenofovir or emtricitabine to pregnant rats; effect on Abcb1a, Abcb1b and Abcg2 expression in the placenta and in maternal and fetal organs

Popis výsledku anglicky

Objectives Tenofovir and emtricitabine are very effective and well-tolerated antiretrovirals representing current backbone of the antiretroviral combination regimens for the prevention of perinatal HIV transmission. The aim of our study was to determine whether tenofovir or emtricitabine administered in long-term fashion affect expression of two widely described pharmacokinetic determinants, P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), in maternal or fetal biological tissues. Methods For this purpose, pregnant Wistar rats were administered tenofovir (2.25 mg/kg/day), emtricitabine (3.5 mg/kg/day) or saline i.m. for 10 days (from the 12th to 21st gestation day). On the 22nd day, the placenta and maternal/fetal intestine, brain, kidneys and liver were sampled and analysed for Abcb1a, Abcb1b and Abcg2 expression; placental and newborns' weights were also monitored. Key findings We found that long-term application of tenofovir or emtricitabine did not significantly affect expression of Abcb1a, Abcb1b and Abcg2 in either maternal or fetal organs. However, tenofovir administration significantly increased placenta-to-birthweight ratio, a strong indicator of various diseases occurring later in life. Conclusions Our data broaden current knowledge on safety profile of tenofovir and emtricitabine use in pregnancy. Nevertheless, further research in other mammal species, including humans, is important to fully elucidate this issue.

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/GAP303%2F12%2F0850" target="_blank" >GAP303/12/0850: Transplacentární farmakokinetika antiretrovirálních léčiv; interakce s efluxními transportéry léčiv</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

Journal of Pharmacy and Pharmacology

ISSN

0022-3573

e-ISSN

—

Svazek periodika

68

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

84-92

Kód UT WoS článku

000368831700009

EID výsledku v databázi Scopus

2-s2.0-84956594370