Photoreactivity of tiaprofenic acid and suprofen using pig skin as an ex vivo model

The skin is repeatedly exposed to solar ultraviolet radiation. Photoreactio n of drugs in the body may result in phototoxic or photoallergic side effec ts. Non-steroidal anti-inflammatory drugs, such as tiaprofenic acid (TPA) a nd the closely related isomer suprofen (SUP) are frequently associated with photosensitive disorders; they may mediate photosensitised damage to lipid s. proteins and nucleic acids. Using ex vivo pig skin as a model, we invest igated the photodegradation of TPA and SUP, and photobinding of these drugs to protein by means of HPLC analysis and drug-directed antibodies. Both wi th keratinocytes, which were first isolated from the pig skin and thereafte r exposed to UVA and with keratinocytes which were isolated from pig skin a fter the skin was UVA exposed, time-dependent photodegradation of TPA and S UP was found, beside photoadduct formation to protein. The results of this work show that: (a) TPA and SUP were photodecomposed with similar efficienc y; major photoproducts detected were decarboxytiaprofenic acid (DTPA) and d ecarboxysuprofen (DSUP), respectively. (b) Both drugs form photoadducts, as concluded from recognition by drug-specific antibodies. Pig skin appears t o be a good model for studying the skin photosensitising potential of drugs . (C) 2000 Elsevier Science B.V. All rights reserved.