COMPARISON OF THE DNA-DAMAGE PHOTOINDUCED BY FENOFIBRATE AND KETOPROFEN, 2 PHOTOTOXIC DRUGS OF PARENT STRUCTURE

Fenofibrate and ketoprofen (KP) are two drugs of similar structure der ived from that of benzophenone. Both are photoallergic and promote cro ss reactions in patients. However, the cutaneous photosensitizing prop erties of KP also include phototoxic effects and are more frequently m entioned. To account for this difference in their in vivo properties, their in vitro photosensitizing properties on DNA were compared. First , it was shown that under irradiation at 313 nm, fenofibric acid (FB), the main metabolite of fenofibrate, photosensitized DNA cleavage by a radical mechanism similar to that proposed for KP but with a 50 times lower efficiency. Furthermore, FB did not photosensitize the formatio n of pyrimidine dimers into DNA in contrast to KP, which did promote t his type of DNA damage. Their difference in efficiency as DNA breakers was compared to their relative photochemical reactivity and the quant um yield of FB photolysis was found to be eightfold lower than that of KP. The reactivity of these drugs cannot explain alone the difference in their photosensitizing properties. Other factors such as the magni tude of the ionic character of the photodecarboxylation pathway of the se benzophenone-like drugs are considered in the discussion.