Abstract

The phototoxic antihyperlipoproteinemic drug fenofibrate (1) is photolabile under aerobic conditions. Irradiation of a methanol solution of 1 produces, under oxygen, photoproducts 2, 3, and 4. A peroxidic photoproduct 2 was isolated and identified. The biologically active antioxidants glutathione and cysteine efficiently reduce 2 to its acid. This photoproduct was also capable of efficiently oxidizing tetramethyl phenylendiamine (TMP) through an electron transfer mechanism, detecting a TMP+ species by UV-visible spectrometry. Fenofibrate was screened in vitro at different concentrations for UV-visible-induced phototoxic effects in a photohemolysis test, under oxygen as well as argon. The photohemolysis rate was low under anaerobic conditions. No hemolysis occurred without irradiation. The isolated photoproduct 2 induced hemolysis without irradiation.

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