Interactions of Potential Anti-COVID-19 Compounds with Multispecific ABC and OATP Drug Transporters

Telbisz, Ágnes; Ambrus, Csilla; Mózner, Orsolya; Szabó, Edit; Várady, György; Bakos, Éva; Sarkadi, Balázs; Özvegy-Laczka, Csilla

doi:10.3390/pharmaceutics13010081

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Interactions of Potential Anti-COVID-19 Compounds with Multispecific ABC and OATP Drug Transporters

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Institute of Enzymology, ELKH Research Centre for Natural Sciences, Magyar Tudósok krt. 2, 1117 Budapest, Hungary

SOLVO Biotechnology, Irinyi József Street 4-20, 1117 Budapest, Hungary

Doctoral School of Molecular Medicine, Semmelweis University, Tűzoltó u. 37-47, 1094 Budapest, Hungary

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Department of Biophysics and Radiation Biology, Semmelweis University, Tűzoltó u. 37-47, 1094 Budapest, Hungary

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Pharmaceutics 2021, 13(1), 81; https://doi.org/10.3390/pharmaceutics13010081

Received: 21 November 2020 / Revised: 28 December 2020 / Accepted: 31 December 2020 / Published: 9 January 2021

(This article belongs to the Special Issue Drug Delivery across Physiological Barriers)

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Abstract

During the COVID-19 pandemic, several repurposed drugs have been proposed to alleviate the major health effects of the disease. These drugs are often applied with analgesics or non-steroid anti-inflammatory compounds, and co-morbid patients may also be treated with anticancer, cholesterol-lowering, or antidiabetic agents. Since drug ADME-tox properties may be significantly affected by multispecific transporters, in this study, we examined the interactions of the repurposed drugs with the key human multidrug transporters present in the major tissue barriers and strongly affecting the pharmacokinetics. Our in vitro studies, using a variety of model systems, explored the interactions of the antimalarial agents chloroquine and hydroxychloroquine; the antihelmintic ivermectin; and the proposed antiviral compounds ritonavir, lopinavir, favipiravir, and remdesivir with the ABCB1/Pgp, ABCG2/BCRP, and ABCC1/MRP1 exporters, as well as the organic anion-transporting polypeptide (OATP)2B1 and OATP1A2 uptake transporters. The results presented here show numerous pharmacologically relevant transporter interactions and may provide a warning on the potential toxicities of these repurposed drugs, especially in drug combinations at the clinic. View Full-Text

Keywords: anti-COVID-19 agents; repurposed drugs; APP-Binding Cassette (ABC) transporters; OATP transporters; in vitro functional studies

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MDPI and ACS Style

Telbisz, Á.; Ambrus, C.; Mózner, O.; Szabó, E.; Várady, G.; Bakos, É.; Sarkadi, B.; Özvegy-Laczka, C. Interactions of Potential Anti-COVID-19 Compounds with Multispecific ABC and OATP Drug Transporters. Pharmaceutics 2021, 13, 81. https://doi.org/10.3390/pharmaceutics13010081

AMA Style

Telbisz Á, Ambrus C, Mózner O, Szabó E, Várady G, Bakos É, Sarkadi B, Özvegy-Laczka C. Interactions of Potential Anti-COVID-19 Compounds with Multispecific ABC and OATP Drug Transporters. Pharmaceutics. 2021; 13(1):81. https://doi.org/10.3390/pharmaceutics13010081

Chicago/Turabian Style

Telbisz, Ágnes, Csilla Ambrus, Orsolya Mózner, Edit Szabó, György Várady, Éva Bakos, Balázs Sarkadi, and Csilla Özvegy-Laczka. 2021. "Interactions of Potential Anti-COVID-19 Compounds with Multispecific ABC and OATP Drug Transporters" Pharmaceutics 13, no. 1: 81. https://doi.org/10.3390/pharmaceutics13010081

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Interactions of Potential Anti-COVID-19 Compounds with Multispecific ABC and OATP Drug Transporters

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