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

Reznicek J, Ceckova M, Cerveny L, Müller F, Staud F (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Xenobiotica Informa Healthcare

Book Volume: 47

Pages Range: 77-85

Journal Issue: 1

DOI: 10.3109/00498254.2016.1158886

Abstract

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 < 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 < 0.01) and augmented intracellular accumulation of emtricitabine (p < 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.

Authors with CRIS profile

Fabian Müller Lehrstuhl für Klinische Pharmakologie und Klinische Toxikologie

Involved external institutions

Univerzita Karlova v Praze / Charles University in Prague CZ Czech Republic (CZ)

How to cite

APA:

Reznicek, J., Ceckova, M., Cerveny, L., Müller, F., & Staud, F. (2017). Emtricitabine is a substrate of MATE1 but not of OCT1, OCT2, P-gp, BCRP or MRP2 transporters. Xenobiotica, 47(1), 77-85. https://doi.org/10.3109/00498254.2016.1158886

MLA:

Reznicek, Josef, et al. "Emtricitabine is a substrate of MATE1 but not of OCT1, OCT2, P-gp, BCRP or MRP2 transporters." Xenobiotica 47.1 (2017): 77-85.

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