title: Penetration kinetics of 8-methoxypsoralen after 8-methoxypsoralen bath procedure with and without UVA irradiation.
abstract: Administration of 8-methoxypsoralen (8-MOP) in a dilute bath water solution is an effective therapeutic alternative for systemic application of 8-MOP, avoiding systemic side effects such as nausea and cataractogenesis. The aim of our study was to determine the epicutaneous penetration of 8-MOP in a dilute bath water solution with and without additional UVA irradiation in human skin under in vitro conditions. To simulate the PUVA bath procedure, 8 skin samples were exposed to radioactively labeled 8-MOP in a water solution. After 20 min, the test solution was removed and the skin surface was dried. Immediately after the bath procedure, 4 of the skin samples were irradiated with 0.5 J/cm2 UVA. During a test period of 15 h, the 8-MOP penetration was observed. In both test groups (with and without UVA irradiation) 8-MOP permeated through all skin layers between 30 min and 1 h after application. Compared to the unirradiated skin samples, the UVA-irradiated skin samples showed a significantly slower increase and a lower maximum of 8-MOP permeation. Following our results, UVA irradiation of 8-MOP-exposed skin samples led to a significantly decreased permeation rate. This might be due to UVA-induced links between 8-MOP molecules and human DNA. In addition, we investigated the levels of radioactivity emitted by tritium-labeled 8-MOP in stratum corneum, epidermis and dermis up to 30 min after 8-MOP bath in two further test groups with and without additional UVA irradiation. The statistical analysis revealed no significant differences between these two test groups. Thus, the levels of radioactivity remained constant in the epidermis and dermis during the test period of 30 min. Since the levels of radioactivity were constant up to 30 min after UVA irradiation, a previously supposed marked loss of 8-MOP concentration might not be responsible for the rapid extinction of observed in vivo photosensitivity within 1 h after PUVA bath observed in vivo in human skin.
authors.affiliation: Department of Dermatology, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: N J
authors.initials: NJ
authors.lastname: Neumann
authors.forename: O J
authors.initials: OJ
authors.lastname: Grosse
authors.forename: T
authors.initials: T
authors.lastname: Ruzicka
authors.forename: P
authors.initials: P
authors.lastname: Lehmann
mesh_terms: D000328:Adult; D020405:Dermis / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008730:Methoxsalen / Q000493:pharmacokinetics*; D012869:Skin Absorption / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D008730:Methoxsalen