金丝桃苷在大鼠体内的药代动力学研究

Pharmacokinetics Study of Hyperoside in Rats

摘要:

目的: 研究金丝桃苷灌胃给药后在Wistar大鼠体内的吸收、分布和排泄。 方法: 大鼠分别灌胃和静脉注射金丝桃苷,于给药后不同时间收集大鼠血浆、组织和排泄物。生物样品先用β-葡萄糖苷酸酶将样品水解成苷元槲皮素,再以山奈酚为内标,HPLC测定槲皮素浓度并折算成金丝桃苷。 结果: 大鼠灌胃给药12.5,25,50 mg·kg^-1金丝桃苷后测得的t1/2e分别为(3.47±0.76),(3.52±0.87),(4.17±1.02)h;tmax均为0.5 h;C_max分别为(0.528±0.230),(1.136±0.451,(2.033±1.147)mg·L^-1;AUC分别为(2.67±0.28),(4.11±0.37),(6.72±0.83)mg·L^-1·h^-1。C_max和AUC均与剂量呈正相关,相关系数分别为0.998,0.999,表明其消除符合线性动力学特征。与静脉注射相比,大鼠灌胃给药金丝桃苷的绝对生物利用度为26.0%。大鼠灌胃给药25 mg·kg^-1金丝桃苷后0.5,3,6 h的药物组织分布由高到低的顺序大致是胃>肠>肾、肝、肌肉、肺、心>脑、子宫>脾、睾丸>脂肪。排泄试验结果显示,72 h内由尿排出的总量约占给药剂量的(0.71±0.13)%,粪排泄量占所给药剂量的(2.04±0.36)%;给药后24 h内,由胆汁排出的总量约占给药剂量的(1.56±0.22)%。 结论: 灌胃给药后,金丝桃苷在大鼠体内吸收迅速,消除半衰期较长,血液及主要脏器无药物蓄积,金丝桃苷的主要排泄方式不是以原形或苷元(包括苷元的其他糖基化衍生物)形式从尿、粪或胆汁排泄。

Abstract:

Objective:To study the absorption, distribution and excretion of hyperoside after intragastric administration to rats. Method: Hyperoside was fed to rats by intragastric and intravenous administration, respectively. Plasma, tissues and excretion samples were collected at different time. The samples were analyzed by HPLC for the detection of quercetin after enzymatic hydrolysis treatment with combined β-glucuronidase and sulphatase, using kaempferol as internal standard. Result: After intragastric administration of hyperoside (12.5, 25, 50 mg·kg^-1) to rats, the main pharmacokinetic parameters t1/2e was (3.47±0.76), (3.52±0.87), (4.17±1.02) h^-1, respectively; tmax was 0.5 h; C_max was (0.528±0.230), (1.136±0.451), (2.033±1.147) mg·L^-1, respectively; AUC was (2.67±0.28), (4.11±0.37), (6.72±0.83) mg·L^-1·h^-1, respectively. Based on the weighted regression analysis of the pooled data, C_max and AUC values increased as the dose increased in a linear manner (r was 0.998 and 0.999, respectively), consistent with the linear pharmacokinetics. As compared to the intravenous administration at a single dose of (25 mg·kg^-1), the absolute bioavailability after intragastric administration of hyperoside was estimated to be 26.0%. After intragastric administration to rats, the rank order of normalized tissue distribution was stomach>intestines>kidney, liver, muscle, lung, heart>cerebrum, uterus>spleen, testis>fat. After intragastric administration hyperoside (25 mg·kg^-1), excretion amount was only (0.71±0.13)% from urine and (2.04±0.36)% from faeces during 72 h, only (1.56±0.22)% from bile during 24 h, respectively. Conclusion: Hyperoside was rapidly absorbed in rats with a long t1/2e. There was no accumulation in blood and main tissues of hyperoside. The main excretion way of hyperoside was not prototype or glucoside forms from urine, faeces or bile excretion.