Binding of 5-Methoxypsoralen to Blood Fractions

Abstract

The binding of 5-methoxypsoralen (5-MOP) to human serum and blood fractions was studied by equilibrium dialysis associated to high-performance liquid chromatography. 5-MOP serum binding was 95% and kept constant in the range of therapeutic concentrations. Albumin was the main binding protein with one class of binding sites (n = 2.05) and with a moderate affinity constant (K_a = 10,270 M^-1). Free fatty acids (FFA) enhanced 5-MOP binding to albumin. Binding to other proteins, α₁-acid glycoprotein, gamma-globulins and lipoproteins (LDL, HDL, VLDL) also occurred, but was negligible. 5-MOP bound to red blood cells (RBCs) with a binding index (ratio of intra- to extra-globular 5-MOP concentrations) of 3.84 and 1.48 in buffer and plasma, respectively. 5-MOP distribution in blood was simulated. The free fraction of 5-MOP in blood could be increased in hypoalbuminemia, unchanged in acute inflammation, and decreased by FFA.

Chromatographic determination of the association constant between 8-methoxypsoralen and modified β-cyclodextrin: protective effect of hydroxypropyl-β-cyclodextrin on 8-methoxypsoralen toxicity in human keratinocytes

“…Psoralens are regularly used in therapy, in combination with ultraviolet A (UVA) light irradiation to treat skin diseases, such as psoriasis, vitiligo and mycosis fungoides [1][2][3][4][5]. In the skin, the combination of psoralens and UVA, also known PUVA, is a potent modulator of epidermal cell growth and differentiation [6,7].…”