Comprehensive Evaluation of Ocular Toxicity of Topical Levofloxacin in Rabbit and Primate Models

Abstract

Levofloxacin, the L‐isomer of ofloxacin and a potent quinolone with a broad spectrum of antibacterial activity, was evaluated in a series of toxicology studies including acute and chronic dosing in rabbits and primates with intact and injured eyes. No evidence of ocular toxicity was observed in rabbits with intact eyes that were topically instilled with levofloxacin ophthalmic solutions under various treatment regimens, including multiple dosing (four to six times daily) for up to 26 weeks at levofloxacin concentrations from 0.3% to 3%. When rabbits were repetitively instilled (10 times at 30 minute intervals) with 0.3%, 1%, or 3% levofloxacin ophthalmic solutions over a single day, they exhibited no increase in ocular irritation scores, whereas dosing with 10% and 25% levofloxacin produced dose‐dependent increases in ocular discharge, conjunctival injection and edema, corneal edema/fluorescein staining, iridic congestion, and behavioral abnormalities. Healing of 7.5 mm diameter epithelial wounds in rabbi...