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D.L. Skelnik, L.A. Clark, P. Bezwada; Effect of Drug Concentration and Exposure Time of Levofloxacin, Ofloxacin, Ciprofloxacin, Gatifloxacin, and Moxifloxacin on Human Corneal Endothelial Cells and Keratocytes . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4739.
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Purpose: The cytotoxic effects of fluoroquinolones were evaluated in an in vitro study by exposing human corneal stromal keratocyte (HCK) and endothelial cells (HCE) to varying concentrations of levofloxacin, ofloxacin, ciprofloxacin, moxifloxacin, and gatifloxacin. Methods: Semi-confluent human corneal stromal keratocyte and endothelial cell monolayers were used in this study. The cells were exposed to the following drug concentrations: 1 mg/mL, 100 mcg/mL, 10 mcg/mL, 1 mcg/mL, 100 ng/mL and 10 ng/mL. At each drug concentration, the cells were incubated for 15 min, 30 min, 1 hour, and 4 hours. Live cells were then quantitated using a calcein AM fluorescent bioassay. Results: Ciprofloxacin was cytotoxic to both HCK and HCE cells at all concentrations and exposure times studied. At clinically relevant MIC levels (1 mcg/mL for most ocular pathogens), gatifloxacin, moxifloxacin and ciprofloxacin were significantly cytotoxic to endothelial cells even at an exposure time of 15 minutes when compared to a minimal essential medium control. Similar results were obtained with keratocytes except for gatifloxacin which was toxic at an exposure time of 30 minutes but not at 15 minutes. Levofloxacin was cytotoxic to both HCK and HCE cells with 1 mcg/mL at 1 hour. Conclusions: The results indicate that the fluoroquinolones have both time- and concentration-related toxic effects on both human corneal stromal keratocyte and endothelial cells. Among the fluoroquinolones that were studied, levofloxacin was found to be less cytotoxic to both human corneal endothelial cells and keratocytes, followed by ofloxacin, gatifloxacin, and moxifloxacin, while ciprofloxacin was found to be the most cytotoxic.
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