Effect of diclofenac on ocular levels of ciprofloxacin and lomefloxacin in rabbits with endophthalmitis

Abstract

The purpose of this study was to analyze ciprofloxacin and lomefloxacin penetration into the anterior eye tissues after topical instillation in healthy rabbits and with experimental Staphylococcus aureus endophthalmitis. Additionally, effect of diclofenac sodium eye drops on the distribution of both fluoroquinolones in the inflamed eye tissues was investigated. An intense protocol with frequent antibiotic administration was chosen. Samples from aqueous humor were obtained 2 and 6 h after the start of the treatment. Samples from cornea and iris were obtained at the end of the experiment, after euthanasia of the animals. Drug concentrations were measured by HPLC method. The median levels of ciprofloxacin and lomefloxacin in aqueous humor of healthy animals, 2 and 6 h after drug administration were 6.39–9.65 and 5.30–6.81 µg/ml, respectively. Ciprofloxacin levels were neither changed from the inflammation nor after instillation of diclofenac. In contrary, lomefloxacin concentrations in aqueous humour of inflamed eye were significantly increased 12.15–15.08 µg/ml, especially after diclofenac administration (17.12–27.76 µg/ml). Levels of both fluoroquinolones in cornea (13.08 µg/g for ciprofloxacin and 12.25 µg/g for lomefloxacin) and in iris (0.84 µg/g for ciprofloxacin and 1.34 µg/g for lomefloxacin) were higher than MIC and MBC values against S. aureus ATCC 25923. Although higher lomefloxacin concentrations were observed in the aqueous humor after instillation of diclofenac, the levels of both fluoroquinolones in iris and in cornea were not significantly changed. Topical administration of lomefloxacin and diclofenac in combination improved penetration of the antibacterial agent in the aqueous humor which can be of clinical importance.