Human aqueous humor concentrations of besifloxacin, moxifloxacin, and gatifloxacin after topical ocular application

• Published in: Journal of cataract and refractive surgery Vol. 37; no. 6; pp. 1082 - 1089
• Main Authors: Donnenfeld, Eric D., MD, Comstock, Timothy L., OD, MS, Proksch, Joel W., PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2011; Elsevier
• Subjects: Administration, Topical; Aged; Aged, 80 and over; Anti-Infective Agents - pharmacokinetics; Aqueous Humor - metabolism; Aza Compounds - pharmacokinetics; Azepines - pharmacokinetics; Biological and medical sciences; Biological Availability; Chromatography, Liquid; Female; Fluoroquinolones - pharmacokinetics; Humans; Male; Medical sciences; Microbial Sensitivity Tests; Middle Aged; Ophthalmic Solutions - pharmacokinetics; Ophthalmology; Quinolines - pharmacokinetics; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the eye and orbit; Tandem Mass Spectrometry; Human; Ocular; Concentration; Aqueous humor; Moxifloxacin; Eye; Local administration; Fluoroquinolone derivatives; Treatment; Gatifloxacin; Surgery; Ophthalmology; Antibacterial agent; Quinolone derivatives; Topical administration
• ISSN: 0886-3350; 1873-4502
• DOI: 10.1016/j.jcrs.2010.12.046

Purpose To determine the concentrations of besifloxacin, moxifloxacin, and gatifloxacin in human aqueous humor after topical instillation of commercially available besifloxacin ophthalmic suspension 0.6%, moxifloxacin ophthalmic solution 0.5%, and gatifloxacin ophthalmic solution 0.3%, and to assess these concentrations relative to the minimum inhibitory concentration for 90% of strains (MIC90 ) for each drug against bacterial pathogens identified in recent cases of postoperative endophthalmitis. Setting Six clinical sites, United States. Design Randomized open-label controlled clinical trial. Methods The aqueous humor drug concentrations were compared 60 minutes ± 5 minutes after instillation of 1 topical drop to patients aged 18 years or older having uncomplicated cataract surgery. Concentrations of besifloxacin, moxifloxacin, and gatifloxacin were determined using a validated liquid chromatography with tandem mass spectrometry method. Results A total of 105 patients were randomized, and aqueous humor samples were analyzed for 103 patients. Mean aqueous humor concentrations were 0.13 μg/mL ± 0.58 (SD), 0.67 ± 0.50 μg/mL, and 0.13 ± 0.08 μg/mL for besifloxacin, moxifloxacin, and gatifloxacin, respectively. Both besifloxacin and moxifloxacin achieved aqueous humor concentrations equal to or slightly higher than their respective MIC90 for methicillin-resistant and methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis; none of the fluoroquinolones achieved concentrations above their MIC90 for ciprofloxacin-resistant strains of S aureus and S epidermidis. Conclusions Based on the aqueous humor drug concentrations measured in this study, it is unlikely that any of the fluoroquinolones tested would be therapeutically effective in the aqueous humor against the most frequently identified drug-resistant staphylococcal isolates from recent cases of postoperative endophthalmitis. Financial disclosure No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes.