Abstract

Phototoxicity, the adverse skin reaction induced by the combination of a chemical and ultraviolet (UV) or visible light, poses a significant challenge in drug development and safety assessment. In this study, we aimed to systematically characterize the photochemical and pharmacokinetic properties of orally administered chemicals to assess their phototoxic risk. To achieve this, we employed a comprehensive set of in vitro and in vivo experiments, utilizing state-of-the-art analytical techniques and predictive models. Our research involved the investigation of the potential of orally administered chemicals to undergo photochemical reactions upon exposure to UV or visible light. We evaluated their absorption, distribution, metabolism, and excretion (ADME) properties to gain insights into their fate within the human body and how these properties might influence their phototoxic potential. Furthermore, we assessed the potential of these chemicals to induce phototoxicity through in vitro and in vivo studies. These studies included dermal cell-based assays, animal models, and human clinical data, enabling us to correlate phototoxic effects with the pharmacokinetic properties of the chemicals. The results of our research revealed significant correlations between the photochemical properties and the likelihood of inducing phototoxicity. We identified key structural and physicochemical characteristics that can be used as indicators for phototoxic risk assessment during drug development. By integrating this information into the early stages of drug design and evaluation, we can enhance the safety of orally administered drugs and reduce the occurrence of phototoxic adverse events in patients. This study represents a valuable contribution to the field of phototoxicity assessment and offers a robust framework for the evaluation of the phototoxic risk associated with orally administered chemicals, thereby improving the overall safety profile of pharmaceutical products.