Abstract
Bromfenac [2-amino-3-(4-bromobenzoyl) benzeneacetic acid sodium slat sesquihydrate] is an anti-inflammatory/analgesic agent that possesses potent topical activity in rats, guinea pigs, and mice. In rat models of acute (carrageenan paw edema) and chronic (adjuvant arthritis) inflammation, preparations of bromfenac at concentrations as low as 0.01–0.32% (0.01–0.32 mg bromfenac) produced significant anti-inflammatory activity when applied to the injected paw or to the backs of rats. In the acute paw edema test, topical bromfenac was more potent than indomethacin or hydrocortisone and about as active as triamcinolone acetonide. Bromfenac, at concentrations of 0.1–0.32%, showed topical analgesic more potent than indomethacin (24.9×), more potent than ketoprofen (⊂14.9×), and superior to piroxicam. In the guinea pig UV-erythema test, bromfenac was active (26.1×indomethacin) when applied to the UV-exposed site, but not when applied away from the site. The results suggest that bromfenac has activity topically because of a local and a systemic effect. Test results obtained with a long (4–7 hr) pretreatment time (paw edema, adjuvant arthritis, abdominal constriction) are due in great part to a systemic effect of topically applied bromfenac, while the UV-erythema test (1-hr treatment time) clearly indicates a local effect.
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D. A. Walsh, H. W. Moran, D. A. Shamblee, I. M. Uwaydah, W. J. Welstead Jr., L. F. Sancilio and W. N. Danenberg,Anti-inflammatory agents. 3. synthesis and pharmacological evaluation of 2-amino-3 benzoylphenylacetic acid and analogues. J. Med. Chem.27, 1379–1380 (1984).
L. F. Sancilio, J. C. Nolan, L. E. Wagner and J. W. Ward,The analgesic and anti-inflammatory activity and pharmacologic properties of bromfenac. Arzneim.-Forsch/Drug Res.37 (1), 513–519 (1987).
B. Silvestrini, V. Cioli and S. Burberi,Pharmacological properties of bendazac (AF 983) with particular reference to its topical action on some experimental inflammatory processes. Arzneim.-Forsch (Drug Res.)20, 250–253 (1970).
H. M. Leibowitz, W. J. Ryan, A. Kupferman and L. DeSantis,Bioavailability and corneal anti-inflammatory effect of topical suprofen. Invest. Opth. Vis. Sci.27, 628–631 (1986).
G. B. Fregnan, A. L. Torsello and S. Brunet,Local anti-inflammatory properties of etoclofene, A new fenamate derivative. Pharmacology11, 213–219 (1974).
R. R. Brooks, K. R. Bonk, G. E. Decker and K. E. Miller,Anti-inflammatory activity of orpanoxin administered orally and topically to rodents. Agents and Actions16, 369–376 (1985).
M. Poisson, C. Ralombosoa, H. Blehaut and J. Astoin, Comparison of the concentration-effect relationship of a local anti-inflammatory agent and oral Acetylsalicylic Acid: The value of local application. Arzneim.-Forsch./ Drug Res.35, 1550–1552 (1985).
D. L. Larson and J. G. Lombardino,The Topical anti-inflammatory effects of Piroxicam in rodents. Agents and Actions10, 246–251 (1980).
Unpublished observations made in the Drug Metabolism Department. A. H. Robins Co.
C. A. Winter, E. A. Risley and G. W. Nuss,Carrageenan-induced edema in hind paw of the rat as an assay for anti-inflammatory drugs. Proc. Soc. Exptl. Biol. Med.111, 544–547 (1962).
D. T. Walz, M. J. Dimartino and A. Misher,Adjuvant-induced arthritis in rats. II. Drug effects on physiologic, biochemical and immunologic parameters. J. Pharmacol. Exp. Ther.178, 223–231 (1971).
L. F. Sancilio, D. L. Reese, S. Cheung and R. S. Alphin, AHR-5850:A potent anti-inflammatory compound. Agents and Actions7, 133–144 (1977).
C. W. Dunnett,A multiple comparison procedure for comparing several treatments with a control. J. Amer. Stat. Assoc.50, 1096–1121 (1955).
A. Goldstein,Biostatistics, An Introductory Text, pp. 102–110. Macmillan Co., New York, 1964.
J. T. Lichfield, and F. Wilcoxon,A simplified method of evaluating dose-effect experiments. J. Pharmacol. Exptl. Ther.96, 99–113 (1949).
C. Bliss,Vitamin Methods, vol. 2 (Ed. E. György), pp. 445–610, Academic Press, New York 1951.
A. P. Green, F. R. Mangan, M. J. Thompson, K. E. Randall and E. A. Boyle,BRL.-20459, A novel topically active nonsteroidal anti-inflammatory drug. J. Pharm. Pharmacol36, 314–317 (1984).
S. I. Naito and Y. H. Tsai,Percutaneous absorption of indomethacin from ointment bases in rabbits. International J. Pharmaceutics8, 263–276 (1981).
P. Schiantarelli, S. Cadel, D. Acerbi and L. Pavesi,Antiinflammatory activity and bioavailability of percutaneous piroxicam. Arzneim.-Forsch/Drug Res.32, 230–235 (1982).
R. Ballerini, A. Casini, M. Chinoi, C. Mannucci, L. Giaccai and M. Salvi,Study on the absorption of ketoprofen topically administered in man: Comparison between tissue and plasma levels. Int. J. Clin. Pharm. Res.VI, 69–72 (1986).
E. Law and A. J. Lewis,The effect of systemically and topically applied drugs on ultraviolet-induced erythema in the rat. Br. J. Pharmac.59, 591–597 (1977).
A. Boris and J. F. Hurley,Assessment of topical anti-inflammatory activity in rats with cantharidin-induced inflammation. J. Invest. Dermat.68, 161–164 (1977).
D. S.-L. Chow, I. Kawa and T. I. Wang,Concentration-dependent enhancement of 1-dodecylazacycloheptan 2-one on the percutaneous penetration kinetics of triomcinolone acetonide. J. Pharm. Sci.73 (12), 1794–1799 (1984).
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Nolan, J.C., Wagner, L.E., Gathright, C.E. et al. The topical anti-inflammatory and analgesic properties of bromfenac in rodents. Agents and Actions 25, 77–85 (1988). https://doi.org/10.1007/BF01969098
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DOI: https://doi.org/10.1007/BF01969098