5-Methoxypsoralen 20mg tablets

Spectroradiometry, radiometry, and dosimetry are employed for the measurement of ultraviolet radiation (UVR) irradiance and non-ionizing exposure. Different types of UVR dosimeter have been developed for measuring personal and environmental UVR exposures since film dosimetry was pioneered in the 1970s. An important type of dosimeter is the thin film variant, which contains materials that undergo changes in optical absorbance when exposed to UVR. These changes can be measured at a specific wavelength using a spectrophotometer. Thin film dosimeters allow UVR exposure measurements on humans at various body sites during daily activities, as well as on plants, animals, and any sites of interest when utilized in a field environment. This review examines the properties and applications of five types of thin film UVR dosimeter that have different dynamic exposure limits and spectral responses. Polysulphone, with a spectral response approximating the human erythema action spectrum, was one of the first materials employed in thin film form for the measurement of UVR exposures up to 1 day, and up to 6 days with an extended dynamic range filter. Polyphenylene oxide has been characterized and employed for personal UVR exposure measurements up to approximately four summer days and has also been used for long-term underwater UVR exposures. Phenothiazine and 8-methoxypsoralen have been reported as suitable for the measurement of longer wavelength UVA exposures. Finally, polyvinyl chloride with an extended dynamic exposure range of over 3 weeks has been shown to have predominantly a spectral response in the UVB and extending up to 340 nm.

Abstract licence: CC BY-NC-ND

This study provides a comprehensive computational exploration of the inhibitory activity and metabolic pathways of 8-methoxypsoralen (8-MP), a furocoumarin derivative used for treating various skin disorders, on cytochrome P450 (P450). Employing quantum chemical DFT calculations, molecular docking, and molecular dynamics (MD) simulations analyses, the biotransformation mechanisms and the active site binding profile of 8-MP in CYP1B1 were investigated. Three plausible inactivation mechanisms were minutely scrutinized. Further analysis explored the formation of reactive metabolites in subsequent P450 metabolic processes, including covalent adduct formation through nucleophilic addition to the epoxide, 8-MP epoxide hydrolysis, and non-CYP-catalyzed epoxide ring opening. Special attention was paid to the catalytic effect of residue Phe268 on the mechanism-based inactivation (MBI) of P450 by 8-MP. Energetic profiles and facilitating conditions revealed a slight preference for the C4'=C5' epoxidation pathway, while recognizing a potential kinetic competition with the 8-OMe demethylation pathway due to comparable energy demands. The formation of covalent adducts via nucleophilic addition, particularly by phenylalanine, and the generation of potentially harmful reactive metabolites through autocatalyzed ring cleavage are likely to contribute significantly to P450 metabolism of 8-MP. Our findings highlight the key role of Phe268 in retaining 8-MP within the active site of CYP1B1, thereby facilitating initial oxygen addition transition states. This research offers crucial molecular-level insights that may guide the early stages of drug discovery and risk assessment related to the use of 8-MP.

Abstract licence: CC BY

Extracorporeal Photopheresis (ECP) is a leukapheresis based treatment for Cutaneous T-Cell Lymphoma, which takes advantage of the cellular lethal effects of UVA light in combination with a photoactivated drug, 8-methoxypsoralen. 25% of patients treated with ECP do not respond to treatment, however the underlying mechanisms for this lack of response remain unknown. Platelets, a rich source of extracellular vesicles (EVs) and key mediators in thromboinflammatory oncological progression, as well as leukocytes, are both processed through ECP and are subsequently transfused back into the patient, delivering potent immunomodulation. The effect of exposing platelets and their EVs directly to Ultra Violet A light (UVA)/8-methoxypsoralen is currently unknown. Platelet-rich plasma (PRP) was isolated from healthy donors and exposed to UVA light and/or 8-methoxysporalen in vitro and platelet activation and aggregation was assessed. EV size and concentration were also characterised by Nanoparticle Tracking Analysis and Flow Cytometry. We found that UVA light and 8-methoxypsoralen treatment in vitro does not induce platelet aggregation or significantly alter levels of the platelet activation markers, soluble P-selectin or platelet factor 4, with circulating levels of small and large EV size and concentration remaining constant. Therefore, utilising the combination of UVA light and 8-methoxypsoralen used in ECP in vitro does not activate platelets or alter important circulating EVs. Further studies will be needed to validate if our observations are consistent in vivo.

Abstract licence: CC BY