PSORALENS PERCUTANEOUS PERMEATION ACROSS THE HUMAN WHOLE SKIN AND THEEPIDERMIS IN RESPECT TO THEIR POLARITY (IN-VITRO STUDY)

8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP) and 4,5',8-trimet hylpsoralen (TMP) are commonly used in PUVA therapy [psoralen (P) + ul traviolet light A (UVA) irradiation] to treat skin diseases such as ps oriasis and vitiligo. In order to predict the choice of the suitable d rug(s) for topical applications, with appropriate dosage, percutaneous permeation of the psoralens, in connection with their solubilities an d partition coefficients in an octanol/water system, were investigated . The percutaneous penetration experiments were accomplished by the de posit of ethanolic psoralen solution onto human skin and epidermis fra gments mounted on Franz(R) cells. Six cells were employed for each pso ralen solution and for the whole skin layer as well as for the epiderm is. The diffused psoralens in the receptor solution (1.4% of human ser um albumin) were quantified by using high performance liquid chromatog raphy. The solubilities and the partition coefficients (PC) were carri ed out in an octanol/water system, in triplicate by using spectrofluor imetry. The results demonstrated that cumulated permeated quantities ( ng/cm(2)) over 24 h, across the whole skin and the epidermis were in t he following order for the three psoralens: 8-MOP > 5-MOP > TMP. The l ipophilicity, expressed via the log PC, was as follows: 1.93 +/- 0.01 (8-MOP), 2.00 +/- 0.01 (5-MOP) and 3.14 +/- 0.01 (TMP). II was inverse ly correlated with cumulated penetrated amounts over 24 h in both whol e skin and epidermis. From these results, TMP could be predicted as th e most convenient psoralen for topical applications, because of its we ak penetrability. Considering the relationship between psoralens lipop hilicity and permeation, only 5-MOP and 8-MOP could be used, topically or orally, especially in the case of generalised skin disorders. Copy right (C) 1997 Elsevier Science Ireland Ltd.