目的 研究黃芩苷對大鼠體內(nèi)硝苯地平藥動學(xué)以及大鼠肝微粒體CYP3A活性的影響。方法 雄性Wistar大鼠分別ig 0.2、0.6 g/kg黃芩苷和硝苯地平10 mg/kg,采用LC-MS法測定血漿中硝苯地平的質(zhì)量濃度,比較藥動學(xué)參數(shù)。黃芩苷和硝苯地平經(jīng)大鼠肝微粒體共孵育后,LC-MS法測定孵育液中氧化硝苯地平的質(zhì)量濃度,比較CYP3A活性。結(jié)果 ig 0.6、0.2 g/kg黃芩苷后,硝苯地平質(zhì)量濃度-時間曲線下面積(AUC_0-t)均顯著增大,表現(xiàn)為硝苯地平的生物利用度升高。黃芩苷0.6 g/kg組硝苯地平的達峰濃度(C_max)顯著升高、藥物清除率(CLz)和表觀分布容積(Vz)顯著降低。黃芩苷0.2 g/kg組硝苯地平的上述藥動學(xué)參數(shù)無顯著變化。30、90μg/mL黃芩苷可降低大鼠肝微粒體孵育體系中氧化硝苯地平的生成量,抑制大鼠肝微粒體CYP3A活性。結(jié)論 黃芩苷可改變大鼠體內(nèi)硝苯地平藥動學(xué)特征,提高生物利用度,這與黃芩苷對CYP3A活性的抑制作用有關(guān)。

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.