An approach to evaluate metabolite-related phototoxicity with combined use of photochemical properties and skin deposition

• A photosafety evaluation system of a chemical and its metabolites is required. Imipramine metabolite, desipramine, were employed as model compounds. Their was assessed based on the photochemical skin exposure data. The outcomes showed great contribution metabolite to phototoxicity. comprehensive evaluations would provide reliable information. Some chemicals have been reported cause metabolite-related phototoxicity, this study aimed verify applicability assessment pharmacokinetic properties evaluate phototoxicity risk. phototoxic risk imipramine (IMI) desipramine (DMI), evaluated by analyses. IMI DMI found similar photoreactivities generation reactive oxygen species. concentrations reached maximal levels at approximately 1 4 h, respectively, after oral administration (10 mg/kg), high deposition compared with IMI. According results, identified contributor induced orally-taken In in vivo testing, ultraviolet irradiation from 3 6 h (100 mg/kg) caused more potent reactions that 0 yielded metabolism be associated orally-administered addition data IMI, parent chemical, profiling DMI, led prediction Thus, characterization generate information chemicals, proposed strategy may facilitate drug candidates pharmaceutical development.