Entecavir Interacts with Influx Transporters hOAT1, hCNT2, hCNT3, but Not with hOCT2: The Potential for Renal Transporter-Mediated Cytotoxicity and Drug-Drug Interactions

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F16%3A00458481" target="_blank" >RIV/61388963:_____/16:00458481 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11160/16:10326203

Result on the web

<a href="http://journal.frontiersin.org/article/10.3389/fphar.2015.00304/full" target="_blank" >http://journal.frontiersin.org/article/10.3389/fphar.2015.00304/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fphar.2015.00304" target="_blank" >10.3389/fphar.2015.00304</a>

Result language

angličtina

Original language name

Entecavir Interacts with Influx Transporters hOAT1, hCNT2, hCNT3, but Not with hOCT2: The Potential for Renal Transporter-Mediated Cytotoxicity and Drug-Drug Interactions

Original language description

Entecavir (ETV) is one of the most potent agents for the treatment of the hepatitis B viral infection. The drug is principally eliminated by the kidney. The goal of this study was to investigate the potential of ETV to interact in vitro with the renal SLC transporters hOAT1, hOCT2, hCNT2 and hCNT3. Potential drug drug interactions of ETV at the renal transporters with antiviral drugs known to be excreted by the kidney (adefovir, tenofovir, cidofovir) as well as transporter-dependent cytotoxicity were also examined. Interactions with the selected transporters along with cytotoxicity were studied in several transiently transfected cellular models using specific substrates and inhibitors. ETV was found to be both a substrate and inhibitor of hOAT1 (IC50 = 175.3 mu M), hCNT2 (IC50 = 241.9 mu M) and hCNT3 (IC50 = 278.4 mu M) transporters, although it interacted with the transporters with relatively low affinities. ETV inhibited the cellular uptake of adefovir, tenofovir, and cidofovir by hOAT1; however, effective inhibition was shown at ETV concentrations exceeding therapeutic levels. In comparison with adefovir, tenofovir, and cidofovir, ETV displayed no transporter mediated cytotoxicity in cells transfected with hOAT1, hCNT2, and hCNT3. No significant interaction of ETV with hOCT2 was detected. The study demonstrates interactions of ETV with several human renal transporters. For the first time, an interaction of ETV with the hCNTs was proved. We show that the potency of ETV to cause nephrotoxicity and/or clinically significant drug drug interactions related to the tested transporters is considerably lower than that of adefovir, tenofovir, and cidofovir.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CC - Organic chemistry

OECD FORD branch

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Project

<a href="/en/project/NT12398" target="_blank" >NT12398: Study on relationships between toxicity and transport mechanism of antivirals</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

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

Name of the periodical

Frontiers in Pharmacology

ISSN

1663-9812

e-ISSN

—

Volume of the periodical

6

Issue of the periodical within the volume

Jan 5

Country of publishing house

CH - SWITZERLAND

Number of pages

11

Pages from-to

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UT code for WoS article

000367506000001

EID of the result in the Scopus database

2-s2.0-84962019456