hrvatski

Farmakokinetičke interakcije između varfarina i derivata luteolina pri vezanju na humani serumski albumin

Flavonoids are a class of secondary plant metabolites and are also omnipresent compounds in daily human nutrition by means of fruit and vegetable consumption. Once they enter circulation, a high number of these compounds binds to the IIA binding site of the human serum albumin (HSA), the most abundant protein in human plasma. Warfarin, a clinically important drug with a narrow therapeutic range also binds to the same binding site. Presence of a high flavonoid concentration can theoretically displace warfarin from its HSA binding site and thus increase its active blood circulation and effects. In this research we tested the effect of different saturation levels of the human serum albumin (HSA) IIA binding site by warfarin on its ability to bind luteolin and two luteolin glucosides, luteolin- 6-C-glucoside (isooorientin) and luteolin-7-O- glucoside (cynaroside). The goal of this research was to determine pharmacokinetic interactions between warfarin and luteolin and its glucosides in binding to HSA. The research was conducted by first incubating HSA with a certain amount of warfarin to achieve different saturation levels (0%, 30%, 50%, 75% i 96%) of the IIA binding site. Afterwards, a flavonoid solution was gradually added to the primary solution. Changes in the HSA-flavonoid interactions were fluorimetrically monitored at the wavelengths of flavonoid absorption and emission, λab= 450 nm, λem= 526 nm. The results showed that saturating the IIA HSA binding site with warfarin has little effect on its ability to bind flavonoids and also that warfarin and the examined flavonoids have different binding sites within the IIA subdomain and consequently do not enter into significant pharmacokinetic interactions.

HSA; luteolin

nije evidentirano