Interaction of hydroxychloroquine with pharmacokinetically important drug transporters
(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 th...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
25 September 2020
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| In: |
Pharmaceutics
Year: 2020, Volume: 12, Issue: 10 |
| ISSN: | 1999-4923 |
| DOI: | 10.3390/pharmaceutics12100919 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/pharmaceutics12100919 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/1999-4923/12/10/919 
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| Author Notes: | Johanna Weiss, Gzona Bajraktari-Sylejmani and Walter E. Haefeli |
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| 520 | |a (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. | ||
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