Saïd A, Makki S, Muret P, Humbert P, Millet J
Laboratoire de Pharmacie Galenique, Faculte de Medecine et de Pharmacie, Besancon, France.
J Dermatol Sci. 1997 Feb;14(2):136-44. doi: 10.1016/s0923-1811(96)00561-0.
8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP) and 4,5',8-trimethylpsoralen (TMP) are commonly used in PUVA therapy [psoralen (P) + ultraviolet light A (UVA) irradiation] to treat skin diseases such as psoriasis and vitiligo. In order to predict the choice of the suitable drug(s) for topical applications, with appropriate dosage, percutaneous permeation of the psoralens, in connection with their solubilities and partition coefficients in an octanol/water system, were investigated. The percutaneous penetration experiments were accomplished by the deposit of ethanolic psoralen solution onto human skin and epidermis fragments mounted on Franz cells. Six cells were employed for each psoralen solution and for the whole skin layer as well as for the epidermis. The diffused psoralens in the receptor solution (1.4%, of human serum albumin) were quantified by using high performance liquid chromatography. The solubilities and the partition coefficients (PC) were carried out in an octanol/water system, in triplicate by using spectrofluorimetry. The results demonstrated that cumulated permeated quantities (ng/cm2) over 24 h, across the whole skin and the epidermis were in the following order for the three psoralens: 8-MOP > 5-MOP > TMP. The lipophilicity, 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). It was inversely correlated with cumulated penetrated amounts over 24 h in both whole skin and epidermis. From these results, TMP could be predicted as the most convenient psoralen for topical applications, because of its weak penetrability. Considering the relationship between psoralens lipophilicity and permeation, only 5-MOP and 8-MOP could be used, topically or orally, especially in the case of generalised skin disorders.
8-甲氧基补骨脂素（8-MOP）、5-甲氧基补骨脂素（5-MOP）和4,5',8-三甲基补骨脂素（TMP）常用于光化学疗法[补骨脂素（P）+紫外线A（UVA）照射]，以治疗银屑病和白癜风等皮肤病。为了预测局部应用合适药物的选择及适当剂量，结合补骨脂素在正辛醇/水体系中的溶解度和分配系数，对其经皮渗透情况进行了研究。经皮渗透实验是通过将补骨脂素乙醇溶液涂覆在安装在Franz扩散池上的人体皮肤和表皮碎片上来完成的。每种补骨脂素溶液、全皮层和表皮均使用六个扩散池。通过高效液相色谱法对受体溶液（含1.4%人血清白蛋白）中扩散的补骨脂素进行定量。溶解度和分配系数（PC）在正辛醇/水体系中采用荧光分光光度法进行三次重复测定。结果表明，在24小时内，三种补骨脂素透过全皮层和表皮的累积渗透量（ng/cm²）顺序如下：8-MOP＞5-MOP＞TMP。通过log PC表示的亲脂性如下：1.93±0.01（8-MOP）、2.00±0.01（5-MOP）和3.14±0.01（TMP）。它与24小时内在全皮层和表皮中的累积渗透量呈负相关。根据这些结果，由于TMP的渗透性较弱，可预测其为最适合局部应用的补骨脂素。考虑到补骨脂素亲脂性与渗透性的关系，只有5-MOP和8-MOP可用于局部或口服，尤其是在全身性皮肤病的情况下。
