Binding of 5-methoxypsoralen to blood fractions. Influence of albumin and free fatty acids: an in vitro study.
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.
Muret
P
P
Service de Dermatologie Fonctionnelle, Besançon, France.
Makki
S
S
Urien
S
S
Agache
P
P
Bechtel
P
P
Tillement
J P
JP
D000078223:5-Methoxypsoralen; D001798:Blood Proteins / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000097:blood; D007700:Kinetics; D008074:Lipoproteins / Q000097:blood; D008730:Methoxsalen / Q000031:analogs & derivatives* / Q000378:metabolism; D009961:Orosomucoid / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism*; D005719:gamma-Globulins / Q000378:metabolism
D001798:Blood Proteins; D005227:Fatty Acids; D008074:Lipoproteins; D009961:Orosomucoid; D012709:Serum Albumin; D005719:gamma-Globulins; D000078223:5-Methoxypsoralen; D008730:Methoxsalen