小儿豉翘清热颗粒中 2 种成分在正常及炎症模型大鼠体内的药动学比较研究

Comparative Study on Pharmacokinetics of two components from Xiao’er Chiqiao Qingre granules in Normal and inflammatory rats

关键词:  小儿豉翘清热颗粒  栀子苷  芍药苷  药代动力学

Key words:  Xiao’er Chiqiao Qingre granules  geniposide  paeoniflorin  pharmacokinetics

摘要:

目的 考察小儿豉翘清热颗粒中栀子苷、芍药苷在正常及炎症模型大鼠体内药代动力学行为差异。方法? 20只大鼠随机分为2组,模型组隔天腹腔注射给予 0.5 mg·kg-1 LPS,持续 2 周,构建 SD 大鼠炎症模型,第七次腹腔注射时给予 1 mg·kg-1 LPS。造模同时,正常组给予等剂量生理盐水。造模成功后,正常及炎症模型大鼠分别灌胃小儿豉翘清热颗粒混悬液3.75 g·kg-1,采集血浆样品,经蛋白沉淀-液液萃取方法处理后,运用LC-MS/MS 方法测定栀子苷、芍药苷浓度,Phoenix Winnolin 6.3. 软件计算药代动力学参数。结果? 小儿豉翘清热颗粒灌胃给药后正常及模型大鼠体内栀子苷的AUC0-t 分别为293.36±59.96和 379.57±194.96 μg·L-1·h, Cmax分别为78.15±25.88和82.63±40.45 μg·L-1, Tmax分别为0.60±0.32和0.73±0.38 h, t1/2分别为1.72±0.70 和1.56±0.53 h,CL/F分别为 68.10±13.03 和66.94±36.20 L·h-1·kg-1,V/F分别为168.41±77.55和153.51±106.9 L·kg-1；芍药苷的AUC0-t 分别为162.82±24.41和 138.34±39.54 μg·L-1·h, Cmax分别为35.85±4.31和30.39±8.94 μg·L-1, Tmax分别为0.70±0.47和0.78±0.72 h, t1/2分别为4.61±3.80 和4.10±1.87 h,CL/F分别为 72.52±19.40 和87.57±21.88 L·h-1·kg-1,V/F分别为404.18±163.58和503.29±260.04 L·kg-1。各参数在正常组与模型组之间均无显著性差异。结论? 炎症状态对小儿豉翘清热颗粒给药后大鼠体内栀子苷、芍药苷的动力学行为无显著影响。

Abstract:

OBJECTIVE To investigate pharmacokinetic differences of geniposide and paeoniflorinin in normal and inflammatory rats after Xiao’er Chiqiao Qingre granules (XECQ) administration. METHODS Twenty rats were randomly divided into two groups, rats in the model group were intraperitoneal injected with 0.5 mg·kg-1 LPS every other day for six times and 1 mg·kg-1 LPS at the last time. Rats in the control group received equal dose of physiological saline at all the same time. After two weeks model making, all rats were oral administration with 3.75 g·kg-1 XECQ. Rat plasma samples were then collected at different time points and treated with protein precipitation-liquid-liquid extraction methods for LC-MS/MS analysis to abtain concentration data. The pharmacokinetic parameters were calculated by Phoenix Winnolin 6.3. RESULTS After XECQ administration, the main pharmacokinetic parameters of geniposide in control and model group were obtained as follows: AUC0-t was 293.36±59.96 and 379.57±194.96 μg·L-1·h, Cmax was 78.15±25.88 and 82.63±40.45 μg·L-1, Tmax was 0.60±0.32 and 0.73±0.38 h, t1/2 was 1.72±0.70 and 1.56±0.53 h, CL/F was 68.10±13.03 and 66.94±36.20 L·h-1·kg-1, V/F was 168.41±77.55 and 153.51±106.9 L·kg-1. The main pharmacokinetic parameters of paeoniflorinin in control and model group were obtained as follows: AUC0-t was 162.82±24.41 and 138.34±39.54 μg·L-1·h, Cmax was 35.85±4.31 and 30.39±8.94 μg·L-1, Tmax was 0.70±0.47 and 0.78±0.72 h, t1/2 was 4.61±3.80 and 4.10±1.87 h, CL/F was 72.52±19.40 and 87.57±21.88 L·h-1·kg-1, V/F was 404.18±163.58 and 503.29±260.04 L·kg-1. Compared with the control group, no significant differences in pharmacokinetic parameters of geniposide and paeoniflorin were observed in the model group. CONCLUSION Inflammatory condition may have few effect on pharmacokinetic behaviors of geniposide and paeoniflorin in rats after XECQ administration.