The Effect of the Corneal Epithelium on the Intraocular Penetration of Fluoroquinolone Ophthalmic Solution

Purpose: Pharmacokinetic studies of antibacterial agents for infectious eye diseases have usually been performed on normal rabbit eyes. In this study, the intraocular penetration of fluoroquinolone ophthalmic solutions was determined in normal rabbit eyes and in rabbit eyes that had the corneal epithelium intentionally removed. Methods: We determined the intraocular penetration of ofloxacin (OFLX), levofloxacin (LVFX), and norfloxacin (NFLX), fluoroquinolone ophthalmic solutions that are already on the market and undergoing clinical studies, by injecting 50 μl of each solution into the cul-de-sacs of rabbit eyes three times at 15-min intervals. The drug concentration at 10, 30, 60, 120, and 240 min after final instillation was determined by high-performance liquid chromatography. Results: The maximum concentration in the aqueous humor of normal rabbit eyes was 2.09 ± 1.56 μg/ml (60 min, OFLX), 2.57 ± 1.00 μg/ml (30 min, LVFX), and 0.42 ± μg/ml (120 min, NFLX). The drug concentration in the aqueous humor of eyes with intentionally removed corneal epithelium was 12.50 ± 5.62 μg/ml (30 min, OFLX), 9.02 ± 2.45 μg/ml (60 min, LVFX), and 8.54 ± 5.17 μg/ml (30 min, NFLX). The drug penetration of the eye drops into eyes with removed corneal epithelium was around 6 times (OFLX), 3.5 times (LVFX), and 20 times (NFLX) higher than the penetration into the eye with normal cornea. Conclusion: Among the pharmacokinetic parameters of the three ophthalmic solutions according to the one-compartment model, the maximum concentration in the aqueous and the area under the concentration-time curve in the aqueous tended to be higher in the eyes with intentionally removed corneal epithelia than in those with normal corneas. © Japanese Ophthalmological Society 2004.