In vitro approach to investigating the phototoxicity of the diuretic drug triamterene

Our approach to assessing the photobiological risk of drugs combines photoc hemical and physicochemical studies with in vitro testing on human Serum,; human erythrocytes, lymphocytes and neutrophils. We have used this approach to investigate the photobiological risk of the diuretic drug triamterene, which has shown phototoxic effects in vivo. Photodecomposition studies of t riamterene in methanol, phosphate buffered saline (PBS) solution and human serum, in the presence of oxygen, was followed by UV spectrophotometry and HPLC analysis using a sensitive HPLC method. Its photodegradation was obser ved only under irradiation with UV-B (290-320 nm) light to produce the phot oproduct 2. No photodecomposition was detected under UV-A (320-400 nm) irra diation, yet singlet oxygen was generated. Triamterene shows a photohaemoly tic effect and photoinduced lipid peroxidation. In the presence of oxygen, triamterene was able to induce photohaemolysis of human erythrocytes. The s ame process was observed under an inert atmosphere, although at a significa ntly lower rate. Studies on peripheral blood mononuclear and polymorphonucl ear cells (lymphocytes and neutrophils) demonstrated phototoxicity on these cell lines. (C) 1998 Elsevier Science Ltd. All rights reserved.