HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Ocular penetration and anti-inflammatory activity of ketorolac 0.45% and bromfenac 0.09% against lipopolysaccharide-induced inflammation.

AbstractPURPOSE:
Anti-inflammatory activity of topical nonsteroidal anti-inflammatory drugs is mediated by suppression of cyclooxygenase (COX) isoenzymes. This study compared ocular penetration and inflammation suppression of topical ketorolac 0.45% and bromfenac 0.09% ophthalmic solutions in a rabbit model.
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:
Both ketorolac 0.45% and bromfenac 0.09% effectively suppressed inflammation at peak. At trough, only ketorolac 0.45% effectively suppressed inflammation as measured by FITC-dextran leakage. The difference in inflammation suppression may be due to differences in tissue concentrations and/or greater COX-1 suppression by ketorolac 0.45%.
AuthorsL David Waterbury, Danielle Galindo, Linda Villanueva, Cathy Nguyen, Milan Patel, Lisa Borbridge, Mayssa Attar, Rhett M Schiffman, David A Hollander
JournalJournal 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
PMID21351868 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzophenones
  • Bromobenzenes
  • Dextrans
  • Lipopolysaccharides
  • fluorescein isothiocyanate dextran
  • bromfenac
  • Prostaglandin-Endoperoxide Synthases
  • Fluorescein-5-isothiocyanate
  • Dinoprostone
  • Ketorolac
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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: