Miranda M A, Boscá F, Vargas F, Canudas N
Departamento de Química, Universidad Politécnica de Valencia, Spain.
Photochem Photobiol. 1994 Feb;59(2):171-4. doi: 10.1111/j.1751-1097.1994.tb05018.x.
Fenofibric acid, the major metabolite of fenofibrate, was found to be photolabile. Its irradiation in aqueous solution gave rise to two photoproducts, whose formation involves photodecarboxylation of the dissociated acid to an aryloxy-substituted carbanion, which is directly protonated or, alternatively, undergoes a Wittig rearrangement. A comparative in vitro phototoxicity study has been carried out on the anti-hyperlipoproteinemic drug fenofibrate, its metabolites and the photoproducts of fenofibric acid. Fenofibrate, fenofibric acid and its two photoproducts were found to be active when examined by the photohemolysis test and were able to photosensitize peroxidation of linoleic acid, as evidenced by the UV monitoring of dienic hydroperoxides. In summary, the major metabolite of fenofibrate (fenofibric acid), as well as its photoproducts, are phototoxic in vitro. This behavior can be attributed to the fact that the four compounds retain the benzophenone chromophore present in fenofibrate and is indicative of free radical-mediated photosensitization. In agreement with this rationalization, the metabolites with a reduced ketone functionality exhibit no detectable in vitro phototoxicity.
非诺贝特的主要代谢产物非诺贝酸被发现具有光不稳定特性。其在水溶液中的辐照产生了两种光产物，其形成涉及离解酸的光脱羧反应生成芳氧基取代的碳负离子，该碳负离子可直接质子化，或者发生维蒂希重排。已对降血脂药物非诺贝特、其代谢产物以及非诺贝酸的光产物进行了一项体外光毒性比较研究。通过光溶血试验检测发现，非诺贝特、非诺贝酸及其两种光产物具有活性，并且能够使亚油酸发生过氧化，这可通过对二烯氢过氧化物的紫外监测得到证明。总之，非诺贝特的主要代谢产物（非诺贝酸）及其光产物在体外具有光毒性。这种行为可归因于这四种化合物保留了非诺贝特中存在的二苯甲酮发色团，这表明是自由基介导的光致敏作用。与这种解释一致的是，具有降低的酮官能团的代谢产物在体外未表现出可检测到的光毒性。
