Fourth-Generation Fluoroquinolone Penetration into the Aqueous Humor in Humans

Purpose: To compare the penetration and levels of the fourth-generation fluoroquinolones moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution in the aqueous humor (AH) in humans after topical application with published levels of other available fluoroquinolones under similar dosing conditions. Design: Prospective, randomized, double-masked clinical trial. Participants: Forty-six patients undergoing cataract extraction. Methods: Patients scheduled for routine phacoemulsification and intraocular lens implantation were provided either moxifloxacin 0.5% ophthalmic solution (n = 22) or gatifloxacin 0.3% ophthalmic solution (n = 24) to use 4 times daily the day before surgery plus 1 drop 1 hour before the surgical entry into the anterior chamber on the day of surgery. This regimen simulated a realistic postoperative dosing schedule. Aqueous humor samples were obtained and analyzed by high-pressure liquid chromatography. Aqueous humor fluoroquinolone concentrations were calculated by peak comparison with a known concentration peak for ciprofloxacin that was used as an internal standard. These values were compared with published concentrations of other available fluoroquinolones under similar dosing conditions. Results: The mean age of the moxifloxacin 0.5% group was 67.8±9.7 years, whereas that of the gatifloxacin 0.3% group was 69.9±8.7 years. The moxifloxacin AH concentration was 1.86±1.06 μg/ml, and that of gatifloxacin was 0.94±0.72 μg/ml. This 2-fold difference was statistically significant (P = 0.001). Conclusions: Aqueous humor antibiotic concentrations achieved at the time of cataract surgery after topical application can serve as an effective surrogate for what can be achieved with typical postoperative topical dosing (e.g., 4 times daily). Both fourth-generation fluoroquinolones achieved a greater AH concentration after 4 times daily dosing relative to prior-generation fluoroquinolones. Moxifloxacin 0.5% ophthalmic solution achieved a 2-fold higher aqueous humor concentration than gatifloxacin 0.3% ophthalmic solution. The superior penetration of moxifloxacin into the AH may be attributed partially to its high degree of lipophilicity, greater solubility at neutral pH, and higher concentration in the commercial formulation. The enhanced penetration of moxifloxacin 0.5% ophthalmic solution may provide better protection against ocular infections.