Photoreactivity of tiaprofenic acid and suprofen using pig skin as an ex vivo model.
The skin is repeatedly exposed to solar ultraviolet radiation. Photoreaction of drugs in the body may result in phototoxic or photoallergic side effects. Non-steroidal anti-inflammatory drugs, such as tiaprofenic acid (TPA) and the closely related isomer suprofen (SUP) are frequently associated with photosensitive disorders; they may mediate photosensitised damage to lipids, proteins and nucleic acids. Using ex vivo pig skin as a model, we investigated the photodegradation of TPA and SUP, and photobinding of these drugs to protein by means of HPLC analysis and drug-directed antibodies. Both with keratinocytes, which were first isolated from the pig skin and thereafter exposed to UVA and with keratinocytes which were isolated from pig skin after the skin was UVA exposed, time-dependent photodegradation of TPA and SUP was found, beside photoadduct formation to protein. The results of this work show that: (a) TPA and SUP were photodecomposed with similar efficiency; major photoproducts detected were decarboxytiaprofenic acid (DTPA) and decarboxysuprofen (DSUP), respectively. (b) Both drugs form photoadducts, as concluded from recognition by drug-specific antibodies. Pig skin appears to be a good model for studying the skin photosensitising potential of drugs.
Sarabia
Z
Z
Department of Medicinal Photochemistry, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands.
Hernández
D
D
Castell
J V
JV
van Henegouwen
G M
GM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism*; D000906:Antibodies / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D015603:Keratinocytes / Q000166:cytology; D008954:Models, Biological; D015394:Molecular Structure; D017319:Photosensitizing Agents / Q000737:chemistry / Q000378:metabolism*; D011422:Propionates / Q000737:chemistry / Q000378:metabolism*; D012867:Skin / Q000166:cytology; D013496:Suprofen / Q000737:chemistry / Q000378:metabolism*; D013552:Swine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000906:Antibodies; D018985:Epitopes, B-Lymphocyte; D017319:Photosensitizing Agents; D011422:Propionates; C021270:tiaprofenic acid; D013496:Suprofen