The Effect of Levofloxacin on Wound Healing in Rabbit and Monkey Models

Abstract

Abstract: : Purpose: To evaluate the effect of different concentrations of levofloxacin on wound healing in rabbit and monkey models of epithelial removal. Methods: Male New Zealand White rabbits and cynomolgus monkeys were used. A corneal epithelial wound was created with heptanol. Rabbits and primates were treated four times daily beginning on the day of injury and continuing for the next 4 days with two drops of levofloxacin solution (rabbits: 0.5%, 1.5%, 3%, or 6%; primates: 1.5% or 3%). Evaluations included the effects on corneal haze, edema, and epithelial wound healing. Rabbits were evaluated up to day 5, and primates were evaluated up to day 11 post-wounding. Results: The results of the rabbit studies show that administration of 1.5% levofloxacin did not delay healing of epithelial wounds. Although a slight transient delay in healing was noted following administration of 3% levofloxacin, healing proceeded to completion in 4 days even with continued dosing. Levofloxacin had a dose-dependent potential to result in corneal edema, and possible loss of keratocytes underlying wounds when it was applied to the large epithelial defects. Such changes were most prevalent following administration of formulations containing 3% or 6% levofloxacin. The results obtained in the primate wound healing model were comparable to those in rabbits with regard to wound healing and corneal edema. Histological evaluation of the eyes also confirmed that there was no detrimental effect to the corneal endothelium as a result of treatment with 1.5% or 3% levofloxacin. Conclusions: Adverse effects following the use of 3% levofloxacin in all studies of experimental corneal wounding were limited to transient and slight-to-mild corneal haze. Administration of 1.5% levofloxacin led to no evidence of drug-induced corneal edema, no adverse effects on corneal stromal fibroblasts and no delay in wound-healinhg in either rabbits or monkeys.

Keywords: drug toxicity/drug effects • antibiotics/antifungals/antiparasitics • wound healing