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.
【저자키워드】 Repurposed drugs, anti-COVID-19 agents, APP-Binding Cassette (ABC) transporters, OATP transporters, in vitro functional studies, 【초록키워드】 Chloroquine, COVID-19 pandemic, Ritonavir, Remdesivir, Favipiravir, Toxicity, drug, antimalarial, Repurposed drug, Health, Patient, Interaction, In vitro studies, tissue, drug combination, anticancer, anti-inflammatory compounds, model systems, Effect, Antiviral compound, affected, examined, significantly, the disease, applied, treated, variety, affecting, alleviate, 【제목키워드】 drug, Compound, transporter, Potential, ABC,