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• W3089088198 startingPage "919" @default.
• W3089088198 abstract "(1) Background: Hydroxychloroquine is used to treat malaria and autoimmune diseases, and its potential use against COVID-19 is currently under investigation. Thus far, information on interactions of hydroxychloroquine with drug transporters mediating drug-drug interactions is limited. We assessed the inhibition of important efflux (P-glycoprotein (P-gp), breast cancer resistance protein (BCRP)) and uptake transporters (organic anion transporting polypeptide (OATP)-1B1, OATP1B3, OATP2B1) by hydroxychloroquine, tested its P-gp and BCRP substrate characteristics, and evaluated the induction of pharmacokinetically relevant genes regulated by the nuclear pregnane X (PXR) (CYP3A4, ABCB1) and aryl hydrocarbon receptor (AhR) (CYP1A1, CYP1A2). (2) Methods: Transporter inhibition was evaluated in transporter over-expressing cell lines using fluorescent probe substrates. P-gp and BCRP substrate characteristics were assessed by comparing growth inhibition of over-expressing and parental cell lines. Possible mRNA induction was analysed in LS180 cells by quantitative real-time PCR. (3) Results: Hydroxychloroquine did not inhibit BCRP or the OATPs tested but inhibited P-gp at concentrations exceeding 10 µM. P-gp overexpressing cells were 5.2-fold more resistant to hydroxychloroquine than control cells stressing its substrate characteristics. Hydroxychloroquine did not induce genes regulated by PXR or AhR. (4) Conclusions: This is the first evidence that hydroxychloroquine’s interaction potential with drug transporters is low, albeit bioavailability of simultaneously orally administered P-gp substrates might be increased by hydroxychloroquine." @default.
• W3089088198 created "2020-10-01" @default.
• W3089088198 creator A5003112632 @default.
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• W3089088198 date "2020-09-25" @default.
• W3089088198 modified "2023-09-24" @default.
• W3089088198 title "Interaction of Hydroxychloroquine with Pharmacokinetically Important Drug Transporters" @default.
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• W3089088198 doi "https://doi.org/10.3390/pharmaceutics12100919" @default.
• W3089088198 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7600351" @default.
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• W3089088198 hasPublicationYear "2020" @default.
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