Comparative intraocular penetration of 4 fluoroquinolones after topical instillation

Purpose: To compare the intraocular penetration of 4 fluoroquinolone eye drops after topical instillation into rabbit eyes. Methods: The tested drugs were levofloxacin 1.5% (LVFX), gatifloxacin 0.3%, moxifloxacin 0.5% (MFLX), and besifloxacin 0.6% (BFLX). Forty-eight New Zealand white rabbits were randomly assigned into 2 groups. For group 1 (40 rabbits, 80 eyes), single instillation was performed, and tissue samples were acquired after 0.5, 1, 2, 4, and 6 hours. For group 2 (8 rabbits, 16 eyes), repeated instillation was performed (4 times, every 15 minutes), and tissues were acquired 1 hour after the fourth instillation. The drug concentrations in ocular tissues (cornea, aqueous, conjunctiva, and trisected vitreous) were analyzed with high-performance liquid chromatography. Results: The AUC_{0-6 h} (area under the curve, in microgram.hour/ gram) in group 1 and the mean concentration (in micrograms/gram) in group 2 for LVFX, gatifloxacin 0.3%, MFLX, and BFLX, respectively, were 22.97, 6.44, 13.54, and 3.29 and 22.60, 6.99, 13.69, and 1.91 in cornea; 5.66, 1.43, 3.38, and 0.42 and 5.52, 1.29, 2.47, and 0.19 in aqueous humor; 2.33, 0.91, 2.17, and 9.83 and 4.51, 0.78, 1.48, and 2.09 in bulbar conjunctiva; 0.243, 0.051, 0.134, and 0.018 and 0.182, 0.055, 0.122, and 0.015 in anterior vitreous; none of the drugs achieved enough concentration in equatorial and posterior vitreous. Repeated instillation resulted in approximately 2.1 times greater penetration than single instillation. Conclusions: LVFX and MFLX demonstrated good intraocular penetration particularly in cornea, aqueous humor, and anterior vitreous, and they may be considered the penetrative fluoroquinolones. BFLX showed high concentration in bulbar conjunctiva and may be considered the retentive fluoroquinolone.