黄芩苷对大鼠口服非索非那定的药动学影响

Effects of baicalin on pharmacokinetics of fexofenadine in rats in vivo

关键词:  黄芩苷  非索非那定  药动学  荧光定量  P-糖蛋白

Key words:  baicalin  fexofenadine  pharmacokinetics  real time pcr  P-gp

摘要:

为了研究黄芩苷在大鼠体内对非索非那定药动学及P-gp表达的影响，将SD大鼠36只随机分为A、B、C三组，连续灌胃7天，A组给予黄芩苷200mg/kg，B组蒸馏水空白对照，C组维拉帕米药物对照(10mg/kg)，第8天灌胃后2小时，各组随机取6只大鼠处死，解剖并迅速取出肝脏、空肠，荧光定量PCR测定各组织P-gp的mRNA表达水平。各组另外6只大鼠灌胃后同时给予非索非那定（30mg/kg），按时间点连续采集血样，采用高效液相色谱法测定非索非那定血药浓度。结果表明，黄芩苷对非索非那定的吸收有明显促进作用，主要表现在黄芩苷组非索非那定峰浓度(Cmax)比空白对照组增加17.04%（P<0.05），曲线下面积AUC(0-12)增加19.23%（P<0.05），黄芩苷减少了大鼠空肠和肝脏P-gp蛋白的表达（P<0.05）。结论：黄芩苷能下调大鼠P-gp表达，增加P-gp底物非索非那定在大鼠体内的生物利用度，是一种P-gp抑制剂。

Abstract:

To investigate effects of baicalin on the pharmacokinetics of fexofenadine in rats in vivo, and evaluate the effect of baicalin on expression of P-gp mRNA.36 SD rats were randomly divided into A,B and C groups, rats in A group were administered with baicalin(200mg/kg), B with distilled water and C were verapamil (10mg/kg) for 7 days. On the 8 day, After 2 hours of administering with baicalin,distilled water and verapamil, 6 rats in every group were killed to collected the liver and jejunum. The rest of rats were administered with fexofenadine(30mg/kg) o. The concentrations of fexofenadine in plasma after administration were determined by HPLC and P-gp mRNA expression level of liver and jejunum were evaluated by real time PCR. After administered with baicalin, AUC(0-12) and Cmax of nifedipine were significantly increased which suggested that the bioavailability of nifedipine were obviously increased. The RT-PCR detection indicated that rats administered with baicalin can decrease the P-gp mRNA expression level in liver and jejunum.It is concluded that baicalin is an inhibitor of P-gp, and it can enhance the bioavailability of nifedipine and decrease the P-gp mRNA expression level significantly