Concentrations of mitomycin C in rabbit corneal tissue and aqueous humor after topical administration

Abstract

Purpose: To study the aqueous and corneal pharmacokinetics of mitomycin C (MMC) after single topical administration to the central cornea and to evaluate the effects of different concentrations and different application times on the aqueous concentration of MMC.

Methods: Mechanical epithelium debridement of the central 7.5 mm of the cornea was performed in New Zealand white rabbits, and a sponge soaked in 0.02% MMC solution was placed on the denuded corneal stroma for 2 minutes. Aqueous fluid and central corneal tissues samples were taken at 0.5, 1, 2, and 3 hours thereafter. MMC concentration of the samples was analyzed by high-performance liquid chromatography and evaluated at different exposure times (range: 15-120 seconds) and concentrations of applied MMC (range: 0.005%-0.04%).

Results: Peak corneal concentration was 3.728 +/- 2.547 microg/g at 30 minutes after topical administration. Maximum aqueous concentration was 0.380 +/- 0.038 microg/mL at 1 hour after topical application. The aqueous concentration of MMC increased in a dose-dependent manner with increasing exposure time and application concentration. Aqueous MMC concentration increased at a higher rate with change of applied concentration than with exposure time.

Conclusion: Good penetration of MMC through central bare cornea may be noxious to endothelial cells. Reducing concentration or decreasing exposure time seems a good modality to reduce potential MMC toxicity.