Pharmacokinetics of Isofraxidin in Extracellular Fluids of Striatum in Rats Using Microdialysis-UPLC Method

Abstract

This study aimed to observe the pharmacokinetic characteristics of isofraxidin in extracellular fluids of striatum in rats after oral administration of isofraxidin. Microdialysis and UPLC-MS analytical technology were used in this study to detect the concentration of isofraxidin in microdialysis dialysate of extracellular fluids of striatum in rats, within 60 min after a single oral administration, with isofraxidin of 10 and 20 mg/kg, respectively. The results were revised by relative recovery in vivo. The pharmacokinetic parameters were calculated through noncompartment model method with software of WINONLIN 6.1 program. The main pharmacokinetic parameters of isofraxidin in extracellular fluids of striatum in rats after a single oral administration of isofraxidin at 10 mg/kg and 20 mg/kg were AUC_0-∞ (13973.88 ± 1582.984) and (28059.76 ± 4207.66) ng·min/mL; t_1/2 (16.68 ± 0.49) and (17.41 ± 2.88) min; C_max(498.87 ± 64.36) and (899.81 ± 133.22) ng/mL. The t_max of both two groups was 15 min. Both the C_max and t_max were measured. It was concluded that isofraxidin quickly permeates the bloodbrain barrier and reaches the striatum. The maximal concentration of isofraxidin is 15 min after oral administration. And then the concentration decreases at a faster rate. It showed a significant dose-dependent phenomenon of the concentration of isofraxidin in extracellular fluids of striatum in rats.