Corneal Penetration and Changes in Corneal Permeability of Moxifloxacin versus Gatifloxacin

Abstract

Abstract: : Purpose:To compare the effects upon the cornea of moxifloxacin versus gatifloxacin by determining their corneal penetration and change in corneal epithelial permeability following exposure to fluoroquinolone solutions in ex vivo corneal perfusion models. Methods:The penetration studies were conducted with solutions of the fluoroquinolones (0.1mM), and the permeability studies were conducted with the commercial preparations: Vigamox^TM (0.5% moxifloxacin, Alcon Laboratories, Inc.) which does not contain BAC, and Zymar^TM (0.3% gatifloxacin, Allergan, Inc.) which contains 0.005% BAC. In both sets of evaluations, corneas of NZW rabbits were excised and mounted in corneal perfusion chambers according to established methods. The penetration studies were conducted with the fluoroquinolone solutions applied to the epithelial side of the cornea. The rates of accumulation of the fluoroquinolones on the endothelial side of the chamber were determined using HPLC analysis of the perfusates over 5 hours. In the permeability studies, the commercial preparations were applied to the epithelial surface for 5 min. After rinsing, corneas were exposed to carboxyfluorescein (CF) for 5 min and the perfusate collected over 2 hrs. The level of CF in the perfusate was measured by spectrophotometry. Results: Moxifloxacin was found to have an apparent corneal permeability coefficient of 91 x 10^–7 cm/sec, compared to 25 x 10^–7 cm/sec for gatifloxacin. The lag time for the appearance of moxifloxacin on the endothelial side of the cornea was 49 min compared to 99 minutes for gatifloxacin. However, permeability of the cornea to CF was 2.1 pMol/ml/min for Vigamox^TM versus 3.4 pMol/ml/min for Zymar^TM, with peaks of accumulation of 37 pMol/ml for Vigamox^TM versus 60 pMol/ml for Zymar^TM. Conclusions: The apparent corneal penetration coefficient of moxifloxacin is 3.6 x greater than gatifloxacin and its appearance on the endothelial side is 2 x faster than gatifloxacin in the absence of any penetration enhancers such as BAC. Although the drug penetration is greater, the corneal permeability to CF is 1.6 x lower after exposure to Vigamox^TM compared to Zymar^TM, illustrating that Vigamox^TM maintains better corneal integrity. This demonstrates that the superior corneal penetration of moxifloxacin is due to the inherent characteristics of the moxifloxacin molecule, and is not due to changes in the corneal epithelial intercellular (gap) junctions.

Keywords: antibiotics/antifungals/antiparasitics • anterior segment • drug toxicity/drug effects