MOLECULAR MECHANISM OF DRUG PHOTOSENSITIZATION .5. PHOTOHEMOLYSIS SENSITIZED BY SUPROFEN

Red blood cell lysis pbotosensitized by Suprofen (SPF) and the photoly sis of the drug were investigated. The photohemolysis process occurs a t a higher rate in anaerobic than aerobic conditions. The effect of ad ditives demonstrates the involvement of free radicals and, to a lesser extent, singlet oxygen and hydroxyl radicals in the process. Photolys is of the drug at 310-390 nm in deaerated buffered solutions (pH 7.4) leads to a decarboxylation process with the formation of p-ethylphenyl 2-thienyl ketone (I), whereas in aerated solutions formation of photo product I and of the photoproducts p-acetylphenyl 2-thienyl ketone (II ) and p-(1-hydroxyethyl)phenyl-2-thienyl ketone (III) occurs. The phot odegradation products, which were separated and characterized, show a moderate lytic and photolytic activity. The rate of SPF photodegradati on decreases in the presence of oxygen and increases in the presence o f hydrogen donors. The overall results lead us to propose a mechanism of SPF photodegradation and a hemolysis scheme in which cell damage is provoked principally by the direct attack of drug radicals and second arily by singlet oxygen and hydroxyl radicals.