title: Tyrosine kinase inhibitors enhance ciprofloxacin-induced phototoxicity by inhibiting ABCG2.
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.
authors.affiliation: Individualized Medicine Program, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Wash., USA.
authors.forename: Katrina L
authors.initials: KL
authors.lastname: Mealey
authors.forename: Sandamali
authors.initials: S
authors.lastname: Dassanayake
authors.forename: Neal S
authors.initials: NS
authors.lastname: Burke
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D015153:Blotting, Western; D002939:Ciprofloxacin / Q000009:adverse effects*; D017484:Dermatitis, Phototoxic / Q000209:etiology*; D004357:Drug Synergism; D005434:Flow Cytometry; D000077156:Gefitinib; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D000068877:Imatinib Mesylate; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D012307:Risk Factors
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D001549:Benzamides; D009363:Neoplasm Proteins; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011799:Quinazolines; D002939:Ciprofloxacin; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib