关键词: 非布司他, 药代动力学, 高效液相, 荧光法

Abstract: AIM: To study the pharmacokinetics of febuxostat tablets and establish an HPLC method for determining the contents of the febuxostat in human plasma. METHODS: 12 healthy volunteers were used 3×3 simplified Latin square design. The volunteers divided into 3 groups were administrated with single dose febuxostat 40, 80, 120 mg respectively, then 80 mg a day for seven days.The plasma concentration of the drug were determined by HPLC-FLU method.Methanol: the mobile phase was 0.1% formic acid (gradient,V/V:0-5.2 min = 71∶29,7-10 min = 90∶10, 10.2-12.5 min = 71∶29). The flow rate was 1.0 mL/min.The excitation wavelength and emission wavelength were 320 nm and 380 nm, respectively. Internal standard was 2 - carboxylic acid. RESULTS: The linear ranges of febuxostat was 0.025-10 mg/L (r=0.9996),the detection limit was 0.005 mg/L,the average recovery was 94.3%,both the RSD for intra-day and inter-day were 1.53%,2.27%.Among 12 healthy subjects,the main pharmacokinetic parameters of febuxostat in single dose of 40、80、120 mg were as follows:C_max=(1.63±0.54),(3.59±1.23),(4.76±1.15) mg/L, t_max=(1.29±0.60),(1.06±0.68),(1.71±0.98) h, AUClast= (4.94±1.21),(11.68 ±2.80),(18.93±5.27) mg·h·L^-1;The pharmacokinetic parameters of multi-dose administration(80 mg) were C_max=(4.19±1.44) mg/L, t_max=(1.31±0.97) h, AUCss=(12.42±3.31) mg·h·L^-1. CONCLUSION: After administration of multi-dose febuxostat, no accumulation occurs in vivo. The pharmacokinetic characteristics of febuxostat tablets were consistent with foreign reports.

Key words: Febuxostat, Pharmacokinetics, HPLC, FLU