PERMEATION CHARACTERISTICS OF 8-METHOXYPSORALEN THROUGH HUMAN SKIN - RELEVANCE TO CLINICAL TREATMENT

The permeation characteristics through human skin of 8-methoxypsoralen (8-MOP) and its physical attributes were investigated. The log octano l/water partition coefficient and saturated aqueous solubility of 8-MO P at 32 degrees C were 1.98 and 55.8 mu g mL(-1) respectively. 8-MOP s howed Fickian diffusion, with its flux being linearly related to the c oncentration of drug in the donor solution. The permeability coefficie nt of 8-MOP through human skin from different concentrations of aqueou s solutions and a 2.6 mu g mL(-1) bath lotion (as used in clinics) wer e statistically identical with mean values of 1.76 +/- 0.12 x 10(-2) a nd 1.70 +/- 0.32 x 10(-2) cm h(-1) respectively (P greater than or equ al to 0.05). An ethanol/water (1:1 w/v) receptor solution did not impr ove the clearance of 8-MOP from the dermis when compared with an aqueo us vehicle. Complete removal of the stratum corneum by tape stripping from full-thickness membranes produced a threefold increase in the flu x of 8-MOP thus suggesting that the main barrier to 8-MOP permeation r esides in the stratum corneum although the aqueous epidermal and derma l tissue provide a significant resistance to transdermal drug permeati on. The equilibrium uptake of 8-MOP into psoriatic plaques and the 8-M OP aqueous/plaque partition coefficient were found to be more than two fold greater than for normal stratum corneum. The absorption of 8-MOP from the total applied topical dose (396 mg) was assessed as similar t o 0.25% and only 25% of an oral dose, a significant reduction in the p ossible toxic hazard. The peak concentration of 8-MOP permeating throu gh 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 sol ution, there may be a need for an interval of about 20 min before pati ents are irradiated to ensure the optimization of photosensitizer with UVA irradiation (PUVA) therapy. Alternatively, UV irradiation could b e applied at a lower Aux over a longer time.