title: Toxicological evaluation of micafungin ophthalmic solution in rabbit eyes.
abstract: There have been no reports of the topical application of micafungin to the eye. The aim of this study was to evaluate the safety of topical instillation of 0.1% micafungin ophthalmic solution in rabbit eyes. In New Zealand white rabbits (n = 6), 50 microL of 0.1% micafungin solution was topically instilled to 1 eye, and 50 microL of sterile saline was applied to the other eye. Both eyedrops were administered hourly from 7 A.M. for 7 days. Measurements were conducted on corneal thickness, intraocular pressure, endothelial cell density, and lactate dehydrogenase (LDH) activity of tear samples. The eyes were examined slit-lamp biomicroscopically and histopathologically. Topical micafungin application for 1 week did not induce any changes in intraocular pressure, endothelial cell density, and tear LDH. Corneal thickness after instillation was slightly, but significantly, smaller in the micafungin group than in the control group (P = 0.0156, paired t test), but this difference disappeared within 24 hours after the final instillation. Biomicroscopy and histopathology revealed no significant toxic influence of micafungin application on the cornea. Topical instillation of micafungin solution had no apparent toxicity to the cornea. These results warrant future studies on the efficacy of micafungin ophthalmic solution against corneal fungal infection.
authors.affiliation: Department of Ophthalmology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. thiraoka@md.tsukuba.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hiraoka
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Wakabayashi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kaji
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Nanbu
authors.forename: Fumiki
authors.initials: F
authors.lastname: Okamoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kiuchi
authors.forename: Beihua
authors.initials: B
authors.lastname: Fu
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Oshika
mesh_terms: D000818:Animals; D002452:Cell Count; D003315:Cornea / Q000187:drug effects* / Q000648:ultrastructure; D054714:Echinocandins; D004728:Endothelium, Corneal / Q000187:drug effects / Q000648:ultrastructure; D007322:Instillation, Drug; D007429:Intraocular Pressure / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D055666:Lipopeptides; D008074:Lipoproteins / Q000633:toxicity*; D008297:Male; D000077551:Micafungin; D046529:Microscopy, Electron, Transmission; D009883:Ophthalmic Solutions; D010456:Peptides, Cyclic / Q000633:toxicity*; D011817:Rabbits; D013666:Tears / Q000187:drug effects* / Q000201:enzymology; D018675:Toxicity Tests
chemical_list: D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D009883:Ophthalmic Solutions; D010456:Peptides, Cyclic; D007770:L-Lactate Dehydrogenase; D000077551:Micafungin