Interactions of protease inhibitors atazanavir and ritonavir with ABCB1, ABCG2, and ABCC2 transporters: Effect on transplacental disposition in rats

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F18%3A10382886" target="_blank" >RIV/00216208:11160/18:10382886 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S0890623818300455" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0890623818300455</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.reprotox.2018.05.008" target="_blank" >10.1016/j.reprotox.2018.05.008</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Interactions of protease inhibitors atazanavir and ritonavir with ABCB1, ABCG2, and ABCC2 transporters: Effect on transplacental disposition in rats

Popis výsledku v původním jazyce

Atazanavir and ritonavir are preferred protease inhibitors frequently used in combination antiretroviral therapy for prevention of HIV mother-to-child transmission. Although their use is associated with higher risk of congenital anomalies, factors affecting atazanavir and ritonavir placental transfer are not known. This study is the first attempt to evaluate whether the placental drug efflux ATP-binding cassette (ABC) transporters, p-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), and/or multidrug resistance-associated proteins 2 (ABCC2), affect placental pharmacokinetics of atazanavir or ritonavir. Transport experiments across MDCKII cells expressing respective human ABC carrier showed that atazanavir is a substrate of ABCB1 and dual perfusion studies in a rat placenta confirmed this finding. In conclusion, we suggest that placental ABCB1 might reduce ATV maternal-to-fetal transfer and therefore represent a site for pharmacokinetic drug-drug interactions of ATV. Further studies in human placenta models are necessary to provide additional data closer to clinical environment.

Název v anglickém jazyce

Interactions of protease inhibitors atazanavir and ritonavir with ABCB1, ABCG2, and ABCC2 transporters: Effect on transplacental disposition in rats

Popis výsledku anglicky

Atazanavir and ritonavir are preferred protease inhibitors frequently used in combination antiretroviral therapy for prevention of HIV mother-to-child transmission. Although their use is associated with higher risk of congenital anomalies, factors affecting atazanavir and ritonavir placental transfer are not known. This study is the first attempt to evaluate whether the placental drug efflux ATP-binding cassette (ABC) transporters, p-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), and/or multidrug resistance-associated proteins 2 (ABCC2), affect placental pharmacokinetics of atazanavir or ritonavir. Transport experiments across MDCKII cells expressing respective human ABC carrier showed that atazanavir is a substrate of ABCB1 and dual perfusion studies in a rat placenta confirmed this finding. In conclusion, we suggest that placental ABCB1 might reduce ATV maternal-to-fetal transfer and therefore represent a site for pharmacokinetic drug-drug interactions of ATV. Further studies in human placenta models are necessary to provide additional data closer to clinical environment.

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

2018

Kód důvěrnosti údajů

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

Název periodika

Reproductive Toxicology

ISSN

0890-6238

e-ISSN

—

Svazek periodika

79

Číslo periodika v rámci svazku

August

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

57-65

Kód UT WoS článku

000439741700008

EID výsledku v databázi Scopus

2-s2.0-85047966943