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L. D. Waterbury, D. Galindo, C. Nguyen, L. Villanueva, M. Patel, L. Borbridge, R. M. Schiffman, D. A. Hollander; Peak and Trough Anti-Inflammatory and Cyclooxygenase (COX) Activity of Ketorolac 0.45% and Bromfenac 0.09%. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1985.
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To compare intraocular concentrations and efficacy of ketorolac 0.45% (AcuvailTM [ket]) to bromfenac 0.09% (Xibrom®[brom]) in a rabbit model of ocular inflammation.
At hour 0, medications (ket, brom, control) were instilled every 20 minutes for 3 doses to 42 New Zealand white rabbits which were then randomized into groups 1 (peak) and 2 (trough). At hour 1, IV lipopolysaccharide (LPS) and a fluorescein isothiocyanate-dextran (FD) marker were administered in group 1. At hour 2, anterior chamber inflammation was evaluated with fluorophotometry and aqueous humor (AH) and iris-ciliary body (CB) samples were collected. In group 2, LPS and FD were administered at hour 10, and measurements and samples were collected at hour 11. Peak and trough concentrations of ket and brom were plotted against COX-1 and COX-2 inhibition curves.
At peak and trough the mean AH concentration of ket was ~8-fold greater than brom. The mean ICB concentration of ket was ~12-fold and 7-fold greater than brom at peak and trough, respectively. At both the peak and trough, respectively, ket (1681 pg/mL, 2250 pg/mL) and brom (1952 pg/mL, 2323 pg/mL) reduced PGE2 relative to vehicle (P < .05). While both ket (0.06 µg/L) and brom (1.05 µg/L) reduced FD leakage at peak (P < .05), only ket (4.7 µg/L), not brom (10.1µg/L), significantly reduced FD leakage relative to vehicle (P < .05) at trough. AH concentrations of ket were ~145X and 25X greater than the IC50 levels for COX-1 and ~24X and ~4X greater than the IC50 levels for COX-2 at peak and trough, respectively. Aqueous concentrations of brom were ~1.3X and 0.24X greater than the IC50 levels for COX-1 and ~42X and ~8X greater than the IC50 levels for COX-2 at peak and trough, respectively.
At peak, both ket and brom significantly reduced inflammation vs vehicle. While both ket and brom also reduced PGE2 levels at hour 11, only ket significantly inhibited FD at trough. Differences in efficacy at trough may be due to insufficient suppression of the COX-1 enzyme by brom.
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