title: Permeation characteristics of 8-methoxypsoralen through human skin; relevance to clinical treatment.
abstract: The permeation characteristics through human skin of 8-methoxypsoralen (8-MOP) and its physical attributes were investigated. The log octanol/water partition coefficient and saturated aqueous solubility of 8-MOP at 32 degrees C were 1-98 and 55.8 micrograms mL-1 respectively, 8-MOP showed Fickian diffusion, with its flux being linearly related to the concentration of drug in the donor solution. The permeability coefficient of 8-MOP through human skin from different concentrations of aqueous solutions and a 2.6 micrograms mL-1 bath lotion (as used in clinics) were statistically identical with mean values of 1.76 +/- 0.12 x 10(-2) and 1.70 +/- 0.32 x 10(-2) cm h-1 respectively (P > or = 0.05). An ethanol/water (1:1 w/v) receptor solution did not improve the clearance of 8-MOP from the dermis when compared with an aqueous vehicle. Complete removal of the stratum corneum by tape stripping from full-thickness membranes produced a threefold increase in the flux of 8-MOP thus suggesting that the main barrier to 8-MOP permeation resides in the stratum corneum although the aqueous epidermal and dermal tissue provide a significant resistance to transdermal drug permeation. The equilibrium uptake of 8-MOP into psoriatic plaques and the 8-MOP aqueous plaque partition coefficient were found to be more than twofold greater than for normal stratum corneum. The absorption of 8-MOP from the total applied topical dose (396 mg) was assessed as approximately 0.25% and only 2.5% of an oral dose, a significant reduction in the possible toxic hazard. The peak concentration of 8-MOP permeating through the skin was observed at about 35 min after limited exposure for 15 min. Our results suggest that following a 15 min bath in the drug solution, there may be a need for an interval of about 20 min before patients are irradiated to ensure the optimization of photosensitizer with UVA irradiation (PUVA) therapy. Alternatively, UV irradiation could be applied at a lower flux over a longer time.
authors.affiliation: Postgraduate Studies in Pharmaceutical Technology, School of Pharmacy, University of Bradford, UK.
authors.forename: A N
authors.initials: AN
authors.lastname: Anigbogu
authors.forename: A C
authors.initials: AC
authors.lastname: Williams
authors.forename: B W
authors.initials: BW
authors.lastname: Barry
mesh_terms: D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008566:Membranes / Q000378:metabolism; D008730:Methoxsalen / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism; D012869:Skin Absorption / Q000502:physiology*; D012995:Solubility
chemical_list: D017319:Photosensitizing Agents; D008730:Methoxsalen