Photosensitivity to ketoprofen - Mechanisms and pharmacoepidemiological data

The topical use of nonsteroidal anti-inflammatory drugs (NSAIDs), widely us ed for moderate acute and chronic painful conditions, is one of several str ategies used to improve the tolerability profile of NSAIDs, particularly wi th regard to gastric and renal adverse effects. However, topical NSAIDs can induce photosensitivity. Among the different NSAIDs used topically, ketopr ofen has often been implicated in photosensitivity reactions. Photosensitiv ity includes both phototoxic and photoallergic reactions. Phototoxicity can be studied in the cell system and on biological targets s uch as cellular membranes or DNA. In hepatocyte cultures, data suggest that radical intermediates play a role in ketoprofen-photosensitised damage by cell membrane lysis. Photosensitised lysis of red blood cells has been empl oyed as an indicator of membrane damage. Ketoprofen irradiation promotes th e photolysis of erythrocyte suspensions. The drug is able to induce photope roxidation of linoleic acid in the photo-induced lipid peroxidation process . The results obtained from the addition of radical scavengers suggest the involvement of free radicals in these processes. Ketoprofen may induce DNA damage in vitro upon irradiation. DNA, in the pre sence of ketoprofen, undergoes single strand breaks involving hydroxyl radi cals as evidenced by the use of scavengers, Simultaneously with single stra nd breaks, pyrimidine dimers are formed by an energy transfer mechanism. Th e oxygen-dependence of both processes suggest competition between a radical process leading to DNA cleavage and a poorly efficient energy transfer bet ween ketoprofen and pyrimidines at the origin of the dimerisation process. Photoallergy is due to a cell-mediated hypersensitivity response involving immunological reactions. Therefore, it only occurs in previously sensitised individuals and requires a latency period of sensitisation. Among NSAIDs, ketoprofen is the main drug involved in this photoallergic contact dermatit is. Cross-sensitivity reactions with other arylpropionic acid derivatives, such tiaprofenic acid, fenofibrate or oxybenzone-harbouring benzoyl ketone or benzophenone may also occur. Finally the higher frequency of such adverse reactions with ketoprofen coul d be accounted for by its chemical structure and the variety of chemical re actions that give rise to phototoxic effects. The widespread and repeated u se of these agents may lead to sensitisation, incurring a greater risk of s ystemic allergic reactions with oral NSAIDs or other drugs recognised to in duce cross-reactions. Physicians and pharmacists should advise patients and inform them of the risks of topical NSAIDs which are often dispensed as ov er the counter drugs.