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


CONCLUSIONS
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.
Song
Jong-Suk
JS
Department of Ophthalmology, Korea University College of Medicine, Seoul, Republic of Korea.
Kim
Jun-Heon
JH
Yang
Minho
M
Sul
Donggeun
D
Kim
Hyo-Myung
HM
D000287:Administration, Topical; D000477:Alkylating Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism*; D003319:Corneal Stroma / Q000187:drug effects; D016685:Mitomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits
D000477:Alkylating Agents; D016685:Mitomycin