Summary and Conclusions
The efficacy of aqueous, oil, and ointment formulations of ketorolac against PGE2-induced ocular inflammation in rabbits was evaluated, with monitoring of blinking rate and PMN and protein migration in tear fluid, following topical PGE2 instillation. Ketorolac ophthalmic formulations protected the eye against inflammatory insult. Chronic topical administration of formulations for 10 days into rats' eyes did not lead to any appreciable gastrointestinal ulceration, which indicates that the formulations are safe for long-term use.
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Footnotes
Department of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences and Research, Formerly College of Pharmacy, University of Delhi, Pushp Vihar, Sector III, New Delhi-110017, India
References
- 1.Hall DWR, Jaitly KD. Inflammatory responses of the rabbit eye to prostaglandins. Agents Actions. 1977;2:123–133. doi: 10.1007/978-3-0348-7177-8_11. [DOI] [PubMed] [Google Scholar]
- 2.Kass MA, Podos SM, Moses RA, Backer B. Prostaglandin E1 and aqueous humor dynamics. Invest Ophthalmol. 1972;11:1022–1027. [PubMed] [Google Scholar]
- 3.Eakins KE. Prostaglandin and non-prostaglandin mediated breakdown of the blood-aqueous barrier. Exp Eye Res. 1977;25:483–498. doi: 10.1016/S0014-4835(77)80043-2. [DOI] [PubMed] [Google Scholar]
- 4.Srinivasan BD, Kulkarni PS. The role of arachidonic acid metabolites in the mediation of the polymorphonuclear leukocyte response following corneal injury. Invest Ophthalmol Vis Sci. 1980;19:1087–1093. [PubMed] [Google Scholar]
- 5.Berman MB, Barber JC, Talamo RC, Langley CE. Corneal ulceration and the serum antiproteases, I: alpha 1-antitrypsin. Invest Ophthalmol. 1973;12:759–770. [PubMed] [Google Scholar]
- 6.Woodward DF, Ledgard SE. Effect of LTD4 on conjunctival vasopermeability and blood aqueous barrier integrity. Invest Ophthalmol Vis Sci. 1985;26:481–485. [PubMed] [Google Scholar]
- 7.Anderson JA, Leopold LH. Antiproteolytic activities found in human tears. Ophthalmology. 1981;88:82–84. doi: 10.1016/S0161-6420(81)35073-8. [DOI] [PubMed] [Google Scholar]
- 8.Rooks WH, Tomolonis AJ, Maloney PJ, Wallach MB, Schuler ME. The analgesic and anti-inflammatory profile of (±)-5-benzoyl-1, 2-dihydro-3H-pyrrolo [1,2a] pyrrole-1-carboxylic acid (RS-37619) Agents Actions. 1982;12:684–690. doi: 10.1007/BF01965079. [DOI] [PubMed] [Google Scholar]
- 9.Flach AJ, Kraff MC, Sanders DR, Tanenbaum L. The quantitative effect of 0.5% ketorolac tromethamine solution and 0.1% dexamethasone sodium phosphate solution on post-surgical blood aqueous barrier. Arch Ophthalmol. 1988;106:480–483. doi: 10.1001/archopht.1988.01060130526028. [DOI] [PubMed] [Google Scholar]
- 10.Heier J, Cheetham JK, Degryse R, et al. Ketorolac tromethamine 0.5% ophthalmic solution in the treatment of moderate to severe ocular inflammation after cataract surgery: a randomized, vehicle-controlled clinical trial. Am J Ophthalmol. 1999;127:253–259. doi: 10.1016/S0002-9394(98)00413-9. [DOI] [PubMed] [Google Scholar]
- 11.Solomon KD, Cheetham JK, Degryse R, Brint SF, Rosenthal A. Topical ketorolac tromethamine 0.5% opthalmic solution in ocular inflammation after cataract surgery. Ophthalmology. 2001;108:331–337. doi: 10.1016/S0161-6420(00)00543-1. [DOI] [PubMed] [Google Scholar]
- 12.Fraser-Smith EB, Mathews TR. Effect of ketorolac on Candida albicans ocular infection in rabbit. Arch Ophthalmol. 1987;105:264–267. doi: 10.1001/archopht.1987.01060020118042. [DOI] [PubMed] [Google Scholar]
- 13.Fraser-Smith EB, Mathews TR. Effect of ketorolac on Pseudomonas aeruginosa ocular infection in rabbits. J Ocul Pharmacol. 1988;4:101–109. doi: 10.1089/jop.1988.4.101. [DOI] [PubMed] [Google Scholar]
- 14.Price FW, Price MO, Zeh W, Dobbins K. Pain reduction after laser in situ keratomileusis with ketorolac tromethamine ophthalmic solution 0.5%: a randomized, double-masked, placebo-controlled trial. J Refract Surg. 2002;18:140–144. doi: 10.3928/1081-597X-20020301-07. [DOI] [PubMed] [Google Scholar]
- 15.Mahoney JM, Waterbury LD. (±)-5-benzoyl-1, 2-dihydro-3H-pyrrolo [1, 2a] pyrrole-1-carboxylic acid (RS-37619): a non-irritating ophthalmic anti-inflammatory agent. Invest Ophthalmol Vis Sci. 1983;24:151–159. [Google Scholar]
- 16.Malhotra M, Majumdar DK. Effect of preservative, antioxidant and viscolizing agents on in vitro transcorneal permeation of ketorolac tromethamine. Indian J Exp Biol. 2002;40:555–559. [PubMed] [Google Scholar]
- 17.Malhotra M, Majumdar DK. In vitro transcorneal permeation of ketorolac from oil based ocular drops and ophthalmic ointment. Indian J Exp Biol. 1997;35:1324–1330. [PubMed] [Google Scholar]
- 18.Malhotra M, Majumdar DK. In vivo ocular availability of ketorolac following ocular instillations of aqueous, oil and ointment formulations to normal corneas of rabbits: a technical note. AAPS Pharm Sci Tech. 2005;6:E523–E526. doi: 10.1208/pt060365. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Pharmacopoeia of India. 2nd ed. Delhi, India: Government of India, Ministry of Health and Family Welfare; 1970:203.
- 20.Abelson MB, Butrus SI, Kliman GH, Larson DL, Corey EJ, Smith LM. Topical arachidonic acid: a model for screening anti-inflammatory agents. J Ocul Pharmacol. 1987;3:63–74. doi: 10.1089/jop.1987.3.63. [DOI] [PubMed] [Google Scholar]
- 21.Sood R. Medical Laboratory Technology: Methods and Interpretations. 4th ed. New Delhi, India: Jaypee Brothers; 1999. pp. 169–237. [Google Scholar]
- 22.Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265–275. [PubMed] [Google Scholar]
- 23.Singh S, Majumdar DK. Evaluation of anti-inflammatory activity of fatty acids of Ocimum sanctum fixed oil. Indian J Exp Biol. 1997;35:380–383. [PubMed] [Google Scholar]
- 24.Maurice DM, Mishima S. Ocular pharmacokinetics. In: Sears ML, editor. Handbook of Experimental Pharmacology: Pharmacology of the Eye. Berlin-Heildelberg, Germany: Springer-Verlag; 1984. pp. 19–103. [Google Scholar]
- 25.Rang HP, Dale MM, Ritter JM, Moore PK. Pharmacology. 5th ed. Edinburgh, Scotland: Churchill Livingstone; 2003. pp. 217–243. [Google Scholar]
- 26.Pillinger MH, Capodici C, Rosenthal P, et al. Modes of action of aspirin-like drugs: salicylates inhibit erk activation and integrin-dependent neutrophil adhesion. Proc Natl Acad Sci USA. 1998;95:14540–14545. doi: 10.1073/pnas.95.24.14540. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Katzung BG. Basic & Clinical Pharmacology. 9th ed. Boston, MA: McGraw-Hill; 2004. pp. 576–603. [Google Scholar]
- 28.Gibaldi M. Biopharmaceutics and Clinical Pharmacokinetics. 3rd ed. Philadelphia, PA: Lea & Febiger; 1984. pp. 85–112. [Google Scholar]