毛蕊花糖苷在常氧、缺氧大鼠体内药动学的比较

In vivo pharmacokinetic comparison of verbascoside in normoxic and hypoxic rats

目的比较毛蕊花糖苷在常氧、缺氧大鼠体内药动学。方法采用低压低氧动物实验舱模拟高原环境制备急性缺氧大鼠模型,常氧、缺氧大鼠灌胃给予毛蕊花糖苷(300 mg/kg),于5、10、15、30、45 min及1、1.5、2、4、6、8、12、24 h采血,HPLC-QTOF-MS法检测毛蕊花糖苷、羟基酪醇、咖啡酸血药浓度,计算主要药动学参数。结果常氧、缺氧大鼠血浆中均未检测到羟基酪醇。与常氧大鼠血浆比较,缺氧大鼠血浆中毛蕊花糖苷AUC_(0~)_(t)、AUC_(0~∞)、C_(max)降低(P<0.05),T_(max)、V_(z)/F升高(P<0.05);咖啡酸AUC_(0~)_(t)、AUC_(0~∞)、C_(max)降低(P<0.05),MRT_(0~∞)、T_(max)、V_(z)/F升高(P<0.05)。结论在缺氧条件下,毛蕊花糖苷及其活性代谢产物咖啡酸的药动学参数发生明显变化。

AIM To compare the in vivo pharmacokinetics of verbascoside in normoxic and hypoxic rats.METHODS The acute hypoxic rat model was established by simulating high-altitude environment in hypobaric hypoxia animal experimental chamber.Normoxic and hypoxic rats were given intragastric administration of verbascoside(300 mg/kg),after which blood collection was made at 5,10,15,30,45 min and 1,1.5,2,4,6,8,12,24 h.HPLC-QTOF-MS was adopted in the plasma concentration determination of verbascoside,hydroxytyrosol and caffeic acid,and main pharmacokinetic parameters were calculated.RESULTS Hydroxytyrosol was not detected in normoxia and hypoxia rat plasma.Verbascoside demonstrated decreased AUC_(0-)_(t),AUC_(0-∞),C_(max)(P<0.05) and increased T_(max),V_(z)/F(P<0.05) in hypoxia rat plasma as compared with those in normoxia rat plasma,along with decreased AUC_(0-)_(t),AUC_(0-∞),C_(max)(P<0.05) and increased MRT_(0-∞),T_(max),V_(z)/F(P<0.05) for caffeic acid.CONCLUSION Under hypoxic condition,the pharmacokinetic parameters for verbascoside and its metabolite caffeic acid exhibit obvious changes.