Concentrations of besifloxacin, gatifloxacin, and moxifloxacin in human conjunctiva after topical ocular administration

ncentrations of besifloxacin, gatifloxacin, and moxifloxacin in human conjunctiva after topical ocular administration Original Research (4699) Total Article Views Authors: Gail Torkildsen, Joel W Proksch, Aron Shapiro, et al Published Date April 2010 Volume 2010:4 Pages 331 - 341 DOI: http://dx.doi.org/10.2147/OPTH.S9163 Gail Torkildsen1, Joel W Proksch2, Aron Shapiro3, Stephanie K Lynch3, Timothy L Comstock2 1Andover Eye Associates, Andover, Massachusetts, USA; 2Bausch and Lomb, Inc., Rochester, New York, USA; 3Ora, Inc., Andover, Massachusetts, USA Purpose: To evaluate the pharmacokinetic properties of besifloxacin, gatifloxacin, and moxifloxacin in the conjunctival tissue of healthy volunteers after topical application. Methods: One-hundred eight (108) subjects were randomly assigned to receive one drop of besifloxacin (0.6% suspension), gatifloxacin (0.3% solution), or moxifloxacin (0.5% solution) ophthalmic formulations in one eye prior to conjunctival biopsy. Conjunctival samples were taken from subjects at either 15 minutes, 30 minutes, 2 hours, 6 hours, 12 hours, or 24 hours after dosing. Results: All three fluoroquinolones reached a peak mean concentration 15 minutes after dosing. The mean concentrations of besifloxacin, gatifloxacin, and moxifloxacin at 15 minutes were 2.30 ± 1.42 μg/g, 4.03 ± 3.84 μg/g, and 10.7 ± 5.89 μg/g, respectively. Concentrations decreased with each subsequent time point. At 24 hours after dosing, concentrations of besifloxacin were measurable in 4 of 6 subjects, compared with 3 of 6 subjects for gatifloxacin and 2 of 6 subjects for moxifloxacin. Besifloxacin had the greatest mean residence time (4.7 hours) in the conjunctival tissue. With regard to methicillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis, besifloxacin had the greatest area-under-the-curve (AUC) to MIC90 ratio. Nine percent (9%) of study subjects (N = 7) experienced a transient reduction in visual acuity. Conclusion: All three fluoroquinolones were well tolerated and reached levels in the conjunctiva above the MIC90s of methicillin-sensitive S. aureus and S. epidermidis for at least 2 hours.