1. Tyrosine Kinase Inhibitors Enhance Ciprofloxacin-Induced Phototoxicity by Inhibiting ABCG2
- Author
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Katrina L. Mealey, Neal S. Burke, and Sandamali Dassanayake
- Subjects
Cancer Research ,animal structures ,Abcg2 ,medicine.drug_class ,Blotting, Western ,Antineoplastic Agents ,Biology ,Pharmacology ,Piperazines ,Tyrosine-kinase inhibitor ,chemistry.chemical_compound ,Gefitinib ,Ciprofloxacin ,Risk Factors ,medicine ,ATP Binding Cassette Transporter, Subfamily G, Member 2 ,Humans ,Protein Kinase Inhibitors ,Drug Synergism ,Retinal ,Imatinib ,General Medicine ,Protein-Tyrosine Kinases ,Flow Cytometry ,Anti-Bacterial Agents ,Neoplasm Proteins ,respiratory tract diseases ,HEK293 Cells ,Pyrimidines ,Gene Expression Regulation ,Oncology ,chemistry ,Benzamides ,embryonic structures ,Imatinib Mesylate ,Quinazolines ,biology.protein ,ATP-Binding Cassette Transporters ,sense organs ,Efflux ,Phototoxicity ,Tyrosine kinase ,Dermatitis, Phototoxic ,medicine.drug - Abstract
The tyrosine kinase inhibitor (TKI) class of anticancer agents inhibits ABCG2-mediated drug efflux. ABCG2 is an important component of the blood-retinal barrier, where it limits retinal exposure to phototoxic compounds such as fluoroquinolone antibiotics. Patients treated with TKIs would be expected to be at greater risk for retinal phototoxicity. Using an in vitro system, our results indicate that the TKIs gefitinib and imatinib abrogate the ability of ABCG2 to protect cells against ciprofloxacin-induced phototoxicity. We conclude that the concurrent administration of ABCG2 inhibitors with photoreactive fluoroquinolone antibiotics may result in retinal damage.
- Published
- 2014
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