BINDING OF 5-METHOXYPSORALEN TO BLOOD FRACTIONS - INFLUENCE OF ALBUMIN AND FREE FATTY-ACIDS - AN INVITRO STUDY

The binding of 5-methoxypsoralen (5-MOP) to human serum and blood frac tions was studied by equilibrium dialysis associated to high-performan ce liquid chromatography. 5-MOP serum binding was 95% and kept constan t in the range of therapeutic concentrations. Albumin was the main bin ding protein with one class of binding sites (n = 2.05) and with a mod erate affinity constant (K(a) = 10,270 M-1). Free fatty acids (FFA) en hanced 5-MOP binding to albumin. Binding to other proteins, alpha1-aci d glycoprotein, gamma-globulins and lipoproteins (LDL, HDL, VLDL) also occurred, but was negligible. 5-MOP bound to red blood cells (RBCs) w ith a binding index (ratio of intra- to extra-globular 5-MOP concentra tions) of 3.84 and 1.48 in buffer and plasma, respectively. 5-MOP dist ribution in blood was simulated. The free fraction of 5-MOP in blood c ould be increased in hypoalbuminemia, unchanged in acute inflammation, and decreased by FFA.