Efficacy of low concentrations of ketorolac tromethamine in animal models of ocular inflammation

Abstract

Abstract: : Purpose: Ketorolac tromethamine is a non–steroidal anti–inflammatory drug (NSAID) that is commercially available both as a 0.5% and a 0.4% ophthalmic solution. This study is designed to determine if topical ophthalmic application of ketorolac tromethamine concentrations below 0.5% can block the biochemical and physiological processes associated with chemically induced ocular inflammation in rabbits. Methods: Ocular inflammation was induced in rabbits by IV injection of endotoxin (2.5 µg/kg) isolated from Salmonella typhimurium or by topical application of arachidonic acid (1.0%). The effect of ketorolac (at concentrations ranging from 0.001% to 0.5%) on ocular inflammation was determined by measuring changes in the blood–aqueous barrier using fluorophotometry (dextran–isothiocyanate–fluorescein; FITC–dextran 2%) and by measuring changes in aqueous humor protein concentrations. Changes in aqueous humor prostaglandin E₂ (PGE₂) concentrations were also measured. Results: Ketorolac 0.01% to 0.5% produced substantial decreases in endotoxin–induced fluorescein leakage into the aqueous humor. The decrease produced by ketorolac 0.1% was comparable to that produced by ketorolac 0.5%. Ketorolac 0.1% to 0.5% produced substantial decreases in endotoxin–induced increases in prostaglandin concentrations in the aqueous humor, and in arachidonic acid–induced protein leakage into the aqueous humor. Conclusions: Topical application of ketorolac concentrations as low as 0.01% to 0.1% significantly reduce chemically induced ocular inflammation in rabbits. Ketorolac formulated at 0.4% should be as effective as ketorolac 0.5% solution for the treatment and prevention of ocular inflammation.

Keywords: pharmacology • inflammation • eicosanoids