In Vitro Approach to investigating the phototoxicity of the diuretic drug triamterene.

ABSTRACT

Our approach to assessing the photobiological risk of drugs combines photochemical 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 triamterene 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 observed only under irradiation with UV-B (290-320nm) light to produce the photoproduct 2. No photodecomposition was detected under UV-A (320-400nm) irradiation, yet singlet oxygen was generated. Triamterene shows a photohaemolytic effect and photoinduced lipid peroxidation. In the presence of oxygen, triamterene was able to induce photohaemolysis of human erythrocytes. The same process was observed under an inert atmosphere, although at a significantly lower rate. Studies on peripheral blood mononuclear and polymorphonuclear cells (lymphocytes and neutrophils) demonstrated phototoxicity on these cell lines.