RESUMEN
Objective:To simulate the occupancy rates of baicalein, quercetin and galangin on the target sites of xanthine oxidase <italic>in vivo</italic>. Method:In this experiment, the half inhibitory concentration (IC<sub>50</sub>) of febuxostat, baicalein, quercetin and galangin against xanthine oxidase were determined by <italic>in vitro</italic> enzymatic reaction. Binding free energy was predicted by molecular docking technology and their association rate constant (k<sub>on</sub>) and dissociation rate constant (k<sub>off</sub>) were determined by surface plasmon resonance technology. Based on measured binding kinetic parameters (k<sub>on</sub> and k<sub>off</sub>) and extracted pharmacokinetic data, the target occupancy model <italic>in vivo</italic> was established. Result:The IC<sub>50 </sub>values of febuxostat, baicalein, quercetin and galangin were 0.002 7, 1.63, 0.38, 1.59 µmol·L<sup>-1</sup>, respectively. The IC<sub>50</sub> of febuxostat was very close to that reported in the literature. The predicted curve of target occupancy rate <italic>in vivo</italic> of febuxostat was consistent with its duration of clinical efficacy. When single intragastric administration of long-circulating liposomes of quercetin with dose of 100 mg·kg<sup>-1</sup> in rats, the time of target occupancy rate >70% <italic>in vivo</italic> lasted for about 3.9 h. When rats were orally administered baicalein and galangin with dose of 200 mg·kg<sup>-1</sup>, the time of target occupancy rate >50% <italic>in vivo </italic>lasted for about 10 h and 1.7 h, respectively. Conclusion:The prediction model of xanthine oxidase target occupancy constructed by drug target binding kinetics and <italic>in vivo</italic> pharmacokinetic curves can effectively evaluate the <italic>in vivo</italic> inhibitory activity of compounds against the target.