THE RELATIONSHIP OF CORNEAL EPITHELIAL DEFECT SIZE TO DRUG PENETRATION

Objective: To determine the relationship between corneal epithelial de fect size and corneal penetration of a triazole antifungal drug in an animal model. Methods: Corneas of adult rabbits were debrided of epith elium 25%, 50%, 75%, or 100% of surface area; the untreated fellow eye served as a control. Tritiated saperconazole was applied to each corn ea every 5 minutes for 1 hour. The animals were killed and the cornea and aqueous of each eye were assayed for radiolabel activity. Results: Removal of 25% of the corneal epithelium produced an increase in corn eal saperconazole concentration compared with eyes with intact epithel ium. Increasing epithelial defect size from 25% to 50% produced a nine fold increase in mean corneal drug concentration (P=.0001). There was no further increase in corneal drug levels in eyes with 75% or 100% ep ithelial defects. A similar threshold effect was observed in aqueous d rug concentration between 25% and 50% debridement (P=.0001). Conclusio n: In this experimental model, an apparent threshold was noted between 25% and 50% epithelial defect area, beyond which larger defects did n ot significantly increase drug penetration into the cornea or aqueous. This may be of clinical benefit in circumstances in which epithelial debridement is considered to enhance drug penetration.