Binding of 5-methoxypsoralen to blood fractions. Influence of albumin and free fatty acids: an in vitro study.

P Muret, S Makki, S Urien, P Agache, P Bechtel, J P Tillement

Index: Skin Pharmacol. 6(1) , 45-51, (1993)

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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 (Ka = 10,270 M-1). Free fatty acids (FFA) enhanced 5-MOP binding to albumin. Binding to other proteins, alpha 1-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.