Interaction of hydroxychloroquine with pharmacokinetically important drug transporters

• Verfasst von: Weiß, Johanna [VerfasserIn]
• Verfasst von: Bajraktari-Sylejmani, Gzona [VerfasserIn]
• Verfasst von: Haefeli, Walter E. [VerfasserIn]
• Titel: Interaction of hydroxychloroquine with pharmacokinetically important drug transporters
• Verf.angabe: Johanna Weiss, Gzona Bajraktari-Sylejmani and Walter E. Haefeli
• E-Jahr: 2020
• Jahr: 25 September 2020
• Umfang: 13 S.
• Teil: volume:12
• Teil: year:2020
• Teil: number:10
• Teil: extent:13
• Fussnoten: Gesehen am 23.11.2020
• Titel Quelle: Enthalten in: Pharmaceutics
• Ort Quelle: Basel : MDPI, 2009
• Jahr Quelle: 2020
• Band/Heft Quelle: 12(2020,10) Artikel-Nummer 919, 13 Seiten
• ISSN Quelle: 1999-4923
• DOI: doi:10.3390/pharmaceutics12100919
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: BCRP
• Sach-SW: drug transporters
• Sach-SW: drug-drug interaction
• Sach-SW: hydroxychloroquine
• Sach-SW: induction
• Sach-SW: inhibition
• Sach-SW: OATP
• Sach-SW: P-glycoprotein
• K10plus-PPN: 1740341007

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.