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L.D. Waterbury; Marked Contralateral Activity of Bromfenac in a Rabbit Model of Ocular Inflammation . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3936.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Both ketorolac and bromfenac are potent anti–inflammatory drugs. In this study we directly compare the ipsilateral anti–inflammatory activities of bromfenac sodium ophthalmic solution 0.1% (XibromTM, Senju Pharmaceuticals, Japan) with those of ketorolac tromethamine 0.4% (Acular LSTM, Allergan Inc, Irvine, CA) in a rabbit model of ocular inflammation. Because contralateral effects have occurred with topical ophthalmic drugs such as timolol, an additional objective was to determine effects of these 2 ophthalmic solutions in the contralateral eye. Methods: In this randomized study, one of the following NSAID solutions was administered to New Zealand white rabbits: ketorolac 0.4% or 0.1% bromfenac. Drug (or vehicle) was administered in 2 single doses (50 µL/dose): the first dose 2 hours before lipopolysaccharide (LPS) endotoxin challenge and second dose 1 hour before LPS challenge with drug administered to one eye and vehicle administered to the contralateral eye. Vehicle consisted of a buffered saline solution. One additional group of rabbits received vehicle without LPS endotoxin. An ocular inflammatory response was induced 1 hour after the last 50–µL dose by the intravenous administration of LPS (10 µg/kg). All rabbits received FITC–dextran (30 mg/kg, i.v.) to monitor the breakdown of the blood–aqueous barrier by fluorophotometry. Comparisons were made between the vehicle treated contralateral eye, and a separate group of vehicle treated rabbits. A t–test assuming unequal variance was used for between–group comparisons. Results: Both bromfenac 0.1% and ketorolac 0.4% resulted in a nearly complete inhibition (98.7% and 99.4% inhibition, respectively) of FITC–dextran in the ipsilateral anterior chamber compared to vehicle treated control rabbits as measured by fluorophotometry of the rabbit eye. Unexpectedly, the mean FITC concentration of the contralateral eyes of the bromfenac–treated rabbits was significantly less than that of rabbits given vehicle only indicating significant (P < .001) contralateral anti–inflammatory activity of bromfenac (79% inhibition) in this model. The mean value of the ketorolac contralateral eyes was not significantly different (P = .178) from rabbits receiving vehicle only. Conclusions: Both ketorolac and bromfenac demonstrated maximal anti–inflammatory activity in this rabbit model of ocular inflammation. Only bromfenac showed a significant (P < .001) contralateral effect suggesting possible systemic effects of bromfenac.
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