4.7 Article

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

期刊

PHARMACEUTICS
卷 13, 期 1, 页码 -

出版社

MDPI
DOI: 10.3390/pharmaceutics13010081

关键词

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

资金

  1. National Research, Development and Innovation Office (OTKA) [FK 128751, K-128011, KFI_16-1-20170232, FIEK 16-1-2016-0005, VEKOP-2.1.1-15-2016-00117]
  2. KDP doctoral scholarship from the Ministry for Innovation and Technology (National Research, Development and Innovation Fund)

向作者/读者索取更多资源

This study examined the interactions of repurposed drugs with key human multidrug transporters, showing numerous pharmacologically relevant transporter interactions that may raise concerns about potential toxicities of these drugs in clinical settings.
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.

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