Emtricitabine is a substrate of MATE1 but not of OCT1, OCT2, P-gp, BCRP or MRP2 transporters

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F17%3A10365387" target="_blank" >RIV/00216208:11160/17:10365387 - isvavai.cz</a>

Result on the web

<a href="http://www.tandfonline.com/doi/full/10.3109/00498254.2016.1158886" target="_blank" >http://www.tandfonline.com/doi/full/10.3109/00498254.2016.1158886</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3109/00498254.2016.1158886" target="_blank" >10.3109/00498254.2016.1158886</a>

Result language

angličtina

Original language name

Emtricitabine is a substrate of MATE1 but not of OCT1, OCT2, P-gp, BCRP or MRP2 transporters

Original language description

1. Emtricitabine is a nucleoside reverse transcriptase inhibitor used in combination antiretroviral therapy of HIV (cART). Although active transport mechanisms are believed to mediate tubular secretion of the drug into urine, the responsible transporter and its potential to cause pharmacokinetic drug-drug interactions (DDI) has not been identified so far. The aim of this study was to investigate whether drug transporters P-gp (ABCB1), BCRP (ABCG2), MRP2 (ABCC2), OCT1 (SLC22A1), OCT2 (SLC22A2) or MATE1 (SLC47A1) can mediate active transcellular transfer of emtricitabine. 2. We employed transport assays in polarized monolayers of MDCK cells stably expressing P-gp, BCRP, MRP2, OCT1, OCT2 and/or MATE1. Among the transporters studied only MATE1 accelerated basal-to-apical transport of emtricitabine over a wide range of concentrations (6 nM to 1 mM). The transport was enhanced by an oppositely directed pH gradient and significantly reduced (p&lt;0.001) at low temperature in MDCK-MATE1, MDCK-OCT1/MATE1 and MDCK-OCT2/MATE1 cells. Co-administration of cimetidine or ritonavir decreased MATE1-mediated transport of emtricitabine by up to 42 and 39%, respectively (p&lt;0.01) and augmented intracellular accumulation of emtricitabine (p&lt;0.05). 3. We demonstrate emtricitabine as a substrate of MATE1 and suggest that MATE1 might cause DDI between emtricitabine and other co-administrated drugs including antiretrovirals.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/GP13-31118P" target="_blank" >GP13-31118P: Interactions of antiretroviral drugs with human drug transporters in vitro in consideration of transplacental pharmacokinetics</a><br>

Continuities

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

Publication year

2017

Confidentiality

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

Name of the periodical

Xenobiotica

ISSN

0049-8254

e-ISSN

—

Volume of the periodical

47

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

9

Pages from-to

77-85

UT code for WoS article

000393948800007

EID of the result in the Scopus database

2-s2.0-84964026690