Abstract | PURPOSE: METHODS: At hour 0, 36 rabbits received ketorolac 0.45%, bromfenac 0.09%, or an artificial tear 3 times once every 20 min. Half of the rabbits in each group then received intravenous injections of lipopolysaccharide (LPS) and fluorescein isothiocyanate ( FITC)-dextran at hour 1, and the other half at hour 10. Aqueous and iris-ciliary body (ICB) samples were collected in the former group at hour 2 (peak) and in the latter group at hour 11 (trough) An additional group of 6 animals received only FITC-dextran, and samples were collected 1 h later. Peak and trough nonsteroidal anti-inflammatory drug concentrations were compared with previously determined half-maximal inhibitory concentrations (IC(50)) for COX isoenzymes. RESULTS: Peak and trough aqueous and ICB concentrations of ketorolac were at least 7-fold or greater than those of bromfenac. At peak levels, both ketorolac 0.45% and bromfenac 0.09% significantly inhibited LPS-induced aqueous prostaglandin E(2) and FITC-dextran elevation (P < 0.01). At trough, both study drugs significantly inhibited LPS-induced aqueous prostaglandin E(2) elevation (P < 0.05), but only ketorolac 0.45% significantly reduced LPS-induced aqueous FITC-dextran elevation (P < 0.01). Aqueous and ICB ketorolac concentrations exceeded its IC(50) for COX-1 and COX-2 at peak and trough. Aqueous and ICB bromfenac levels exceeded its IC(50) for COX-2 at peak and trough, but not for COX-1 at trough aqueous levels and peak and trough ICB levels. CONCLUSIONS:
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Authors | L David Waterbury, Danielle Galindo, Linda Villanueva, Cathy Nguyen, Milan Patel, Lisa Borbridge, Mayssa Attar, Rhett M Schiffman, David A Hollander |
Journal | Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
(J Ocul Pharmacol Ther)
Vol. 27
Issue 2
Pg. 173-8
(Apr 2011)
ISSN: 1557-7732 [Electronic] United States |
PMID | 21351868
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Benzophenones
- Bromobenzenes
- Dextrans
- Lipopolysaccharides
- fluorescein isothiocyanate dextran
- bromfenac
- Prostaglandin-Endoperoxide Synthases
- Fluorescein-5-isothiocyanate
- Dinoprostone
- Ketorolac
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Topics |
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(pharmacology)
- Aqueous Humor
(drug effects, metabolism)
- Benzophenones
(pharmacokinetics, pharmacology)
- Bromobenzenes
(pharmacokinetics, pharmacology)
- Dextrans
(metabolism)
- Dinoprostone
(analysis)
- Endophthalmitis
(drug therapy)
- Eye
(metabolism)
- Female
- Fluorescein-5-isothiocyanate
(analogs & derivatives, metabolism)
- Ketorolac
(pharmacokinetics, pharmacology)
- Lipopolysaccharides
- Prostaglandin-Endoperoxide Synthases
(metabolism)
- Rabbits
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