目的 研究黄芩苷对大鼠体内硝苯地平药动学以及大鼠肝微粒体CYP3A活性的影响。方法 雄性Wistar大鼠分别ig 0.2、0.6 g/kg黄芩苷和硝苯地平10 mg/kg,采用LC-MS法测定血浆中硝苯地平的质量浓度,比较药动学参数。黄芩苷和硝苯地平经大鼠肝微粒体共孵育后,LC-MS法测定孵育液中氧化硝苯地平的质量浓度,比较CYP3A活性。结果 ig 0.6、0.2 g/kg黄芩苷后,硝苯地平质量浓度-时间曲线下面积(AUC_0-t)均显著增大,表现为硝苯地平的生物利用度升高。黄芩苷0.6 g/kg组硝苯地平的达峰浓度(C_max)显著升高、药物清除率(CLz)和表观分布容积(Vz)显著降低。黄芩苷0.2 g/kg组硝苯地平的上述药动学参数无显著变化。30、90μg/mL黄芩苷可降低大鼠肝微粒体孵育体系中氧化硝苯地平的生成量,抑制大鼠肝微粒体CYP3A活性。结论 黄芩苷可改变大鼠体内硝苯地平药动学特征,提高生物利用度,这与黄芩苷对CYP3A活性的抑制作用有关。

Objective To investigate effects of baicalin on the pharmacokinetics of nifedipine in rats in vivo, and evaluate the effect of baicalin on CYP3A activity. Methods Male Wistar rats were ig administered with baicalin (0.2 and 0.6 g/kg) and nifedipine (10 mg/kg), and concentrations of nifedipine in serum were determined by LC-MS method. Meanwhile pharmacokinetic parameters were compared. Nifedipine was incubated with or without baicalin in rat liver microsomes, and oxidized nifedipine in incubation solution was determined by LC/MS method. CYP3A activities were compared among baicalin group and control group. Results After ig administered with baicalin 0.2 and 0.6 g/kg, AUC_0-t of nifedipine were significantly increased which suggested that the bioavailability of nifedipine were obviously increased. C_max of rats in 0.6 g/kg baicalin group were significantly increased, but CLz and Vz were significantly decreased. There were no significant changes of above index of rats in 0.2 g/kg baicalin group. Baicalin with concentrations of 30 and 90 μg/mL could reduce amounts of oxidized nifedipine in incubation solution, inhibit the activities of CYP3A. Conclusion Baicalin can alter the pharmacokinetic characteristic, and increase bioavailability of nifedipine in rats, which may be related to inhibition of CYP3A-mediated metabolism in rat liver microsomes.