Makki S, Muret P, Renaud A, Agache P, Magnin P
Laboratoires de Chimie Analytique et de Dermatologie et Biologie Cutanée, Faculté de Médecine et Pharmacie, Besançon, France.
J Chromatogr. 1991 Feb 22;539(2):443-8. doi: 10.1016/s0021-9673(01)83953-4.
Increasingly used in therapeutics, 5-methoxypsoralen (5-MOP), a linear furocoumarin, associated with UVA irradiation (PUVA), is now an established treatment for skin diseases such as vitiligo, mycosis funcoides and particularly psoriasis. Successful PUVA therapy depends on a sufficiently high peak 5-MOP plasma concentration coinciding with the UVA irradiation. However, as with most drugs, only the free plasma fraction is able to enter the target cells and has a pharmacological effect. In this work, the binding of 5-MOP to human albumin was studied in vitro, using a dialysis chamber. Bound and free 5-MOP fractions were quantified by a modification of Stolk's high-performance liquid chromatographic method. Dialysis was performed at 37 degrees C and pH 7.4 for 2 h, against a 4% albumin solution in phosphate buffer. The 5-MOP concentrations used were from 5 x 10(-5) to 5 x 10(-2) g/l in 1 x 10(-1) g/l steps. The 5-MOP bound strongly to human albumin in an unsaturable way. The mean 5-MOP binding to albumin was 95.3%. These results are in accordance with those published by Artuc et al. and not with those of Veronese et al., who found a lower saturable fixation (91%). These two research groups used tritiated 5-MOP. The technique used in this work is simple and inexpensive. It can be employed easily in vivo, e.g., for the assessment of 5-MOP free fractions in different therapeutic conditions.
5-甲氧基补骨脂素（5-MOP）是一种线性呋喃香豆素，与紫外线A照射（PUVA）联合使用，在治疗中应用越来越广泛，现已成为治疗白癜风、蕈样肉芽肿尤其是银屑病等皮肤病的既定疗法。成功的PUVA疗法取决于与紫外线A照射同时出现的足够高的5-MOP血浆峰值浓度。然而，与大多数药物一样，只有游离血浆部分能够进入靶细胞并产生药理作用。在这项工作中，使用透析室在体外研究了5-MOP与人白蛋白的结合。结合和游离的5-MOP部分通过对斯托尔克高效液相色谱法的改进进行定量。在37℃和pH 7.4条件下，针对磷酸盐缓冲液中的4%白蛋白溶液进行2小时透析。使用的5-MOP浓度以1×10⁻¹g/l的步长从5×10⁻⁵到5×10⁻²g/l。5-MOP以不饱和方式与人白蛋白强烈结合。5-MOP与白蛋白的平均结合率为95.3%。这些结果与阿尔图克等人发表的结果一致，而与韦罗内塞等人的结果不同，后者发现较低的可饱和固定率（91%）。这两个研究小组使用了氚标记的5-MOP。这项工作中使用的技术简单且成本低廉。它可以很容易地用于体内，例如，用于评估不同治疗条件下的5-MOP游离部分。
