Interaction of Hydroxychloroquine with Pharmacokinetically Important Drug Transporters
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Cytotoxicity Assays
2.3. P-gp Inhibition Assay (Calcein-AM Uptake Assay)
2.4. BCRP Inhibition Assay (Flow Cytometric Pheophorbide A Efflux Assay)
2.5. Flow Cytometric OATP1B1 and OATP1B3 Inhibition Assay
2.6. Flow Cytometric OATP2B1 Inhibition Assay
2.7. Growth Inhibition Assays with Resistant Cell Lines for Assessing P-gp and BCRP Substrate Characteristics
2.8. Induction Assay
2.9. Statistical Analyses
3. Results
3.1. Inhibition of Drug Transporters by Hydroxychloroquine
3.2. P-gp and BCRP Substrate Characteristics of Hydroxychloroquine
3.3. Induction of PXR and AhR Regulated Genes by Hydroxychloroquine
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Gene | Forward Primer 5′-3′ | Reverse Primer 5′-3′ | A [°C] | Ref. |
---|---|---|---|---|
ABCB1 | CCCATCATTGCAATAGCAGG | TGTTCAAACTTCTGCTCCTG | 60 | [29] |
ABCG2 | AGATGGGTTTCCAAGCGTTCAT | CCAGTCCCAGTACGACTGTGACA | 57 | [29] |
CYP1A1 | TCCGGGACATCACAGACAGC | ACCCTGGGGTTCATCACCAA | 65 | [31] |
CYP1A2 | CATCCCCACAGCACAACAA | TCCCACTTGGCCAGGACTTC | 63 | [32] |
CYP3A4 | TTCAGCAAGAAGAACAA | GGTTGAAGAAGTCTCTAAGC | 57 | [33] |
GU | TTCACCAGGATCCACCTCTG | AGCACTCTCGTCGGTGACTG | 61 | [34] |
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Weiss, J.; Bajraktari-Sylejmani, G.; Haefeli, W.E. Interaction of Hydroxychloroquine with Pharmacokinetically Important Drug Transporters. Pharmaceutics 2020, 12, 919. https://doi.org/10.3390/pharmaceutics12100919
Weiss J, Bajraktari-Sylejmani G, Haefeli WE. Interaction of Hydroxychloroquine with Pharmacokinetically Important Drug Transporters. Pharmaceutics. 2020; 12(10):919. https://doi.org/10.3390/pharmaceutics12100919
Chicago/Turabian StyleWeiss, Johanna, Gzona Bajraktari-Sylejmani, and Walter E. Haefeli. 2020. "Interaction of Hydroxychloroquine with Pharmacokinetically Important Drug Transporters" Pharmaceutics 12, no. 10: 919. https://doi.org/10.3390/pharmaceutics12100919
APA StyleWeiss, J., Bajraktari-Sylejmani, G., & Haefeli, W. E. (2020). Interaction of Hydroxychloroquine with Pharmacokinetically Important Drug Transporters. Pharmaceutics, 12(10), 919. https://doi.org/10.3390/pharmaceutics12100919