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Benoxaprofen Improves Psoriasis: A Double-blind Study

Benoxaprofen Improves Psoriasis: A Double-blind Study Abstract • The pathophysiologic significance of increased levels of lipoxygenase compounds in psoriatic lesions was assessed in a double-blind randomized clinical study with the 5-lipoxygenase inhibitor, benoxaprofen. Forty patients with psoriasis vulgaris were treated with 600 mg of oral benoxaprofen daily or a placebo for a period of eight weeks. Benoxaprofen therapy provided excellent treatment results in about 75% of the cases. In the placebo group, only minimal improvement occurred. Most patients receiving benoxaprofen therapy reported side effects including photosensitivity, onycholysis, milia, diarrhea, and edema. In two cases, benoxaprofen was withdrawn before completion of the treatment course because of photosensitivity. Benoxaprofen may affect psoriatic epidermis either directly by the inhibition of epidermal 5-lipoxygenase or indirectly by the inhibition of the accumulation of phagocytes in psoriatic lesions. Despite serious side effects from benoxaprofen therapy, lipoxygenase-inhibiting agents deserve further study in the treatment of psoriasis. (Arch Dermatol 1983;119:548-552) References 1. Hammarstrom S, Hamberg M, Samuelsson B, et al: Increased concentrations of nonesterified arachidonic acid, 12-L-hydroxy-5,8,14-eicosatetraenoic acid, prostaglandin E2, prostaglandin F2α in epidermis of psoriasis . Proc Natl Acad Sci USA 1975;72:5130-5134.Crossref 2. Samuelsson B, Goldyne M, Granstrom E, et al: Prostaglandins and thromboxanes . Annu Rev Biochem 1971;47:997-1029.Crossref 3. Borgeat P, Samuelsson B: Arachidonic acid metabolism in polymorphonuclear leukocytes: Effects of ionophore A23187 . Proc Natl Acad Sci USA 1979;76:2148-2152.Crossref 4. Brain SD, Camp RDR, Dowd PM, et al: Psoriasis and leukotriene B4 . Lancet 1982;2:762-763.Crossref 5. Brain SD, Camp RDR, Leigh IM, et al: The synthesis of leukotriene B4-like material by cultured human keratinocytes . J Invest Dermatol 1982;78:328. 6. Ford-Hutchinson AW, Bray MA, Doig MV, et al: Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes . Nature 1980;286:264-265.Crossref 7. Goetzl EJ, Pickett WC: The human PMN leukocyte chemotactic activity of complex hydroxy-eicosatetraenoic acids (HETEs) . J Immunol 1980;125:1789-1791. 8. Nagy L, Lee TH, Goetzl EJ, et al: Complement receptor enhancement and chemotaxis of human neutrophils and eosinophils by leukotrienes and other lipoxygenase products . Clin Exp Immunol 1982;47:541-547. 9. Carr SC, Couts AA, Greaves MW, et al: Responses of human skin to intradermal injection of leukotrienes C4, D4, and B4 . J Invest Dermatol 1982;78:329. 10. Cashin CH, Dawson W, Kitchen EA: The pharmacology of benoxaprofen (2-[4-chlorophenyl]-α-methyl-5-benzoxazole acetic acid), LRCL 3794, a new compound with anti-inflammatory activity apparently unrelated to inhibition of prostaglandin synthesis . J Pharm Pharmacol 1977;29:330-336.Crossref 11. Dawson W, Boot JR, Harvey J, et al: The pharmacology of benoxaprofen with particular reference to effects on lipoxygenase product formation . Eur J Rheumatol Inflam 1982;5:61-68. 12. Meacock SCR, Kitchen EA, Dawson W: Effects of benoxaprofen and other non-steroidal anti-inflammatory drugs on leukocyte migration . Eur J Rheumatol Inflam 1979;3:23-28. 13. Mikulaschek WM: An update on long-term efficacy and safety with benoxaprofen . Eur J Rheumatol Inflam 1982;5:206-215. 14. Hamdy RC, Mumane B, Pesera N, et al: The pharmacokinetics of benoxaprofen in elderly subjects . Eur J Rheumatol Inflam 1982;5:69-75. 15. Halsey JP, Cardoe N: Benoxaprofen: Side-effect profile in 300 patients . Br Med J 1982;284:1365-1368.Crossref 16. Kligman AM, Kaidbey KH: Phototoxicity to benoxaprofen . Eur J Rheumatol Inflam 1982;5:124-137. 17. Ferguson J, Addo HA, McGill PE, et al: A study of benoxaprofen-induced photosensitivity . Br J Dermatol 1982;107:429-442.Crossref 18. Greist MC, Ozols II, Ridolfo AS, et al: The phototoxic effects of benoxaprofen and their management and prevention . Eur J Rheumatol Inflam 1982;5:61-68. 19. Orentbreich N, Harber LC, Tromovitch TA: Photosensitivity and photo-onycholysis due to demthylchlortetracycline . Arch Dermatol 1961;83:730-737.Crossref 20. Taylor AEM, Goff D, Hindson TC: Association between Stevens-Johnson syndrome and benoxaprofen therapy . Br Med J 1981;282:1433.Crossref 21. Fenton DA, English FS: Toxic epidermal necrolysis, leukopenia and thrombocytopenic purpura: A further complication of benoxaprofen therapy . Clin Exp Dermatol 1982;7:277-280.Crossref 22. Essigman WK, Williams FRB: Transient neutropenia due to benoxaprofen . Lancet 1980;2:1383.Crossref 23. Taggart HM, Alderdice FM: Fatal cholestatic jaundice in elderly patients taking benoxaprofen . Br Med J 1982;284:1372.Crossref 24. Lewis RA, Austen KF: Mediation of local homeostasis and inflammation by leukotrienes and other mast cell-dependent compounds . Nature 1981;293:103-108.Crossref 25. Katayama H, Kawada A: Exacerbation of psoriasis induced by indomethacin . J Dermatol 1981;8:323-327. 26. Hammerstrom S, Hamberg M, Duell EA, et al: Glucocorticoid in inflammatory proliferative skin disease reduces arachidonic and hydroxyeicosatetraenoic acids . Science 1977;197:994-996.Crossref 27. Cantiere JS, Graff G, Goldberg ND: Cyclic GMP metabolism in psoriasis: Activation of soluble epidermal guanylate cyclase by arachidonic acid and 12-hydroxy-5,8,10,14-eicosatetraenoic acid . J Invest Dermatol 1980;74:234-237.Crossref 28. Marcelo CL, Duell EA, Stawiski MA, et al: Cyclic nucleotide levels in psoriatic and normal keratomed epidermis . J Invest Dermatol 1979;72:20-24.Crossref 29. Voorhees JJ: Cyclic AMP regulation of normal and psoriatic epidermis . Arch Dermatol 1982;118:869-874.Crossref 30. Jablonska S, Chowaniec O, Bentner EH, et al: Stripping of the stratum corneum in patients with psoriasis: Production of prepinpoint papules and psoriatic lesions . Arch Dermatol 1982;118:652-657.Crossref 31. Whaba A, Cohen HA, Ba-Eli M, et al: Enhanced chemotactic and phagocytic activities of leukocytes in psoriasis vulgaris . J Invest Dermatol 1978;71:186-188.Crossref 32. Krueger GG, Jederberg WW, Ogden BE, et al: Inflammatory and immune cell function in psoriasis: II. Monocyte function, lymphokine production . J Invest Dermatol 1978;71:195-207.Crossref 33. Allen BR, Littlewood SM: Benoxaprofen: Effect on cutaneous lesions in psoriasis . Br Med J 1982;285:1241.Crossref 34. Hindson C, Lawlor F, Wacks H: Treatment of nodular acne with benoxaprofen . Br J Dermatol 1982;107:369-372.Crossref 35. Hindson C, Daymond T, Diffey B, et al: Side effects of benoxaprofen . Br Med J 1982;284:1368-1369.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

Benoxaprofen Improves Psoriasis: A Double-blind Study

Archives of Dermatology , Volume 119 (7) – Jul 1, 1983

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Publisher
American Medical Association
Copyright
Copyright © 1983 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archderm.1983.01650310010002
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Abstract

Abstract • The pathophysiologic significance of increased levels of lipoxygenase compounds in psoriatic lesions was assessed in a double-blind randomized clinical study with the 5-lipoxygenase inhibitor, benoxaprofen. Forty patients with psoriasis vulgaris were treated with 600 mg of oral benoxaprofen daily or a placebo for a period of eight weeks. Benoxaprofen therapy provided excellent treatment results in about 75% of the cases. In the placebo group, only minimal improvement occurred. Most patients receiving benoxaprofen therapy reported side effects including photosensitivity, onycholysis, milia, diarrhea, and edema. In two cases, benoxaprofen was withdrawn before completion of the treatment course because of photosensitivity. Benoxaprofen may affect psoriatic epidermis either directly by the inhibition of epidermal 5-lipoxygenase or indirectly by the inhibition of the accumulation of phagocytes in psoriatic lesions. Despite serious side effects from benoxaprofen therapy, lipoxygenase-inhibiting agents deserve further study in the treatment of psoriasis. (Arch Dermatol 1983;119:548-552) References 1. Hammarstrom S, Hamberg M, Samuelsson B, et al: Increased concentrations of nonesterified arachidonic acid, 12-L-hydroxy-5,8,14-eicosatetraenoic acid, prostaglandin E2, prostaglandin F2α in epidermis of psoriasis . Proc Natl Acad Sci USA 1975;72:5130-5134.Crossref 2. Samuelsson B, Goldyne M, Granstrom E, et al: Prostaglandins and thromboxanes . Annu Rev Biochem 1971;47:997-1029.Crossref 3. Borgeat P, Samuelsson B: Arachidonic acid metabolism in polymorphonuclear leukocytes: Effects of ionophore A23187 . Proc Natl Acad Sci USA 1979;76:2148-2152.Crossref 4. Brain SD, Camp RDR, Dowd PM, et al: Psoriasis and leukotriene B4 . Lancet 1982;2:762-763.Crossref 5. Brain SD, Camp RDR, Leigh IM, et al: The synthesis of leukotriene B4-like material by cultured human keratinocytes . J Invest Dermatol 1982;78:328. 6. Ford-Hutchinson AW, Bray MA, Doig MV, et al: Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes . Nature 1980;286:264-265.Crossref 7. Goetzl EJ, Pickett WC: The human PMN leukocyte chemotactic activity of complex hydroxy-eicosatetraenoic acids (HETEs) . J Immunol 1980;125:1789-1791. 8. Nagy L, Lee TH, Goetzl EJ, et al: Complement receptor enhancement and chemotaxis of human neutrophils and eosinophils by leukotrienes and other lipoxygenase products . Clin Exp Immunol 1982;47:541-547. 9. Carr SC, Couts AA, Greaves MW, et al: Responses of human skin to intradermal injection of leukotrienes C4, D4, and B4 . J Invest Dermatol 1982;78:329. 10. Cashin CH, Dawson W, Kitchen EA: The pharmacology of benoxaprofen (2-[4-chlorophenyl]-α-methyl-5-benzoxazole acetic acid), LRCL 3794, a new compound with anti-inflammatory activity apparently unrelated to inhibition of prostaglandin synthesis . J Pharm Pharmacol 1977;29:330-336.Crossref 11. Dawson W, Boot JR, Harvey J, et al: The pharmacology of benoxaprofen with particular reference to effects on lipoxygenase product formation . Eur J Rheumatol Inflam 1982;5:61-68. 12. Meacock SCR, Kitchen EA, Dawson W: Effects of benoxaprofen and other non-steroidal anti-inflammatory drugs on leukocyte migration . Eur J Rheumatol Inflam 1979;3:23-28. 13. Mikulaschek WM: An update on long-term efficacy and safety with benoxaprofen . Eur J Rheumatol Inflam 1982;5:206-215. 14. Hamdy RC, Mumane B, Pesera N, et al: The pharmacokinetics of benoxaprofen in elderly subjects . Eur J Rheumatol Inflam 1982;5:69-75. 15. Halsey JP, Cardoe N: Benoxaprofen: Side-effect profile in 300 patients . Br Med J 1982;284:1365-1368.Crossref 16. Kligman AM, Kaidbey KH: Phototoxicity to benoxaprofen . Eur J Rheumatol Inflam 1982;5:124-137. 17. Ferguson J, Addo HA, McGill PE, et al: A study of benoxaprofen-induced photosensitivity . Br J Dermatol 1982;107:429-442.Crossref 18. Greist MC, Ozols II, Ridolfo AS, et al: The phototoxic effects of benoxaprofen and their management and prevention . Eur J Rheumatol Inflam 1982;5:61-68. 19. Orentbreich N, Harber LC, Tromovitch TA: Photosensitivity and photo-onycholysis due to demthylchlortetracycline . Arch Dermatol 1961;83:730-737.Crossref 20. Taylor AEM, Goff D, Hindson TC: Association between Stevens-Johnson syndrome and benoxaprofen therapy . Br Med J 1981;282:1433.Crossref 21. Fenton DA, English FS: Toxic epidermal necrolysis, leukopenia and thrombocytopenic purpura: A further complication of benoxaprofen therapy . Clin Exp Dermatol 1982;7:277-280.Crossref 22. Essigman WK, Williams FRB: Transient neutropenia due to benoxaprofen . Lancet 1980;2:1383.Crossref 23. Taggart HM, Alderdice FM: Fatal cholestatic jaundice in elderly patients taking benoxaprofen . Br Med J 1982;284:1372.Crossref 24. Lewis RA, Austen KF: Mediation of local homeostasis and inflammation by leukotrienes and other mast cell-dependent compounds . Nature 1981;293:103-108.Crossref 25. Katayama H, Kawada A: Exacerbation of psoriasis induced by indomethacin . J Dermatol 1981;8:323-327. 26. Hammerstrom S, Hamberg M, Duell EA, et al: Glucocorticoid in inflammatory proliferative skin disease reduces arachidonic and hydroxyeicosatetraenoic acids . Science 1977;197:994-996.Crossref 27. Cantiere JS, Graff G, Goldberg ND: Cyclic GMP metabolism in psoriasis: Activation of soluble epidermal guanylate cyclase by arachidonic acid and 12-hydroxy-5,8,10,14-eicosatetraenoic acid . J Invest Dermatol 1980;74:234-237.Crossref 28. Marcelo CL, Duell EA, Stawiski MA, et al: Cyclic nucleotide levels in psoriatic and normal keratomed epidermis . J Invest Dermatol 1979;72:20-24.Crossref 29. Voorhees JJ: Cyclic AMP regulation of normal and psoriatic epidermis . Arch Dermatol 1982;118:869-874.Crossref 30. Jablonska S, Chowaniec O, Bentner EH, et al: Stripping of the stratum corneum in patients with psoriasis: Production of prepinpoint papules and psoriatic lesions . Arch Dermatol 1982;118:652-657.Crossref 31. Whaba A, Cohen HA, Ba-Eli M, et al: Enhanced chemotactic and phagocytic activities of leukocytes in psoriasis vulgaris . J Invest Dermatol 1978;71:186-188.Crossref 32. Krueger GG, Jederberg WW, Ogden BE, et al: Inflammatory and immune cell function in psoriasis: II. Monocyte function, lymphokine production . J Invest Dermatol 1978;71:195-207.Crossref 33. Allen BR, Littlewood SM: Benoxaprofen: Effect on cutaneous lesions in psoriasis . Br Med J 1982;285:1241.Crossref 34. Hindson C, Lawlor F, Wacks H: Treatment of nodular acne with benoxaprofen . Br J Dermatol 1982;107:369-372.Crossref 35. Hindson C, Daymond T, Diffey B, et al: Side effects of benoxaprofen . Br Med J 1982;284:1368-1369.Crossref

Journal

Archives of DermatologyAmerican Medical Association

Published: Jul 1, 1983

References