PHOTOTOXICITY FROM BENOXAPROFEN: IN VIVO AND IN VITRO STUDIES |
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Authors: | Guy F. Webster Kays H. Kaidbey Albert M. Kligman |
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Affiliation: | Duhring Laboratories, Department of Dermatology, Hospital of the University of Pennsylvania, Medical Education Building/GM, Philadelphia, PA 19104, USA |
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Abstract: | Abstract Benoxaprofen (2-[4-chlorophenyl]-α-methyl-5-benzoxazole acetic acid), a non-steroidal antiinflammatory drug, was found to provoke phototoxicity reactions in humans. Exposure of the skin of benoxaprofen-treated subjects to either solar simulating radiation or a broad UV-A wavelength band produced intense itching and burning sensations, followed by the development of a classical wheal and flare response within 2-4 min. Phototoxicity was related to both the UV radiation fluence and the dose of orally administered benoxaprofen. Wavelengths between 320 and 340nm were active in provoking urticaria. In vitro studies demonstrated that benoxaprofen and UV irradiation produced a dose-dependent lysis of sheep erythrocytes which did not appear to be dependent on the presence of oxygen. Red cells were not lysed by pre-irradiated benoxaprofen arguing against the production of stable lytic photoproducts. Human neutrophils were lysed by benoxaprofen and UV light which resulted in the liberation of both cytoplasmic and lysosomal enzymes. Benoxaprofen failed to induce photolysis of human platelets and photoactivation of complement in human serum. It is suggested that phototoxic urticaria provoked by benoxaprofen may be due to a direct photolytic effect on human dermal mast cells. |
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