Photodegradation of bezafibrate in aqueous media. Studies of its in vitro phototoxicity.
Aqueous solutions of the antihyperlipoproteinemic drug bezafibrate (CAS 41859-67-0) are photolabile towards UV-B light under aerobic conditions. Two compounds were isolated and identified spectroscopically as well as by alternative synthesis as the only photoproducts formed. Their formation involves primary cleavage of the aryloxy-carbon bond and decarboxylation followed by hydrogen abstraction or dimerization. Bezafibrate is phototoxic in vitro as indicated by the photohemolysis test. Furthermore bezafibrate photo-sensitizes peroxidation of linoleic acid as monitored by the UV detection of dienic hydroperoxides. Partial inhibition of these processes on addition of butylated hydroxyanisole (BHA), reduced glutathione (GSH), sodium azide (NaN3) or 1,4-diazabicyclo [2.2.2] octane (DABCO) suggests the involvement of type I as well as type II mechanisms.
Canudas
N
N
Centro de Quimica, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela.
Vargas
F
F
Miranda
M A
MA
D000332:Aerobiosis; D001629:Bezafibrate / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects*; D004912:Erythrocytes / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D000960:Hypolipidemic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects*; D066298:In Vitro Techniques; D008027:Light; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D010777:Photochemistry; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D000960:Hypolipidemic Agents; D008041:Linoleic Acids; D019787:Linoleic Acid; D001629:Bezafibrate