毛蕊花糖苷在大鼠体内吸收、分布及排泄研究

目的:采用液相色谱-质谱联用(LC-MS/MS)法测定大鼠血浆及组织样品中毛蕊花糖苷的浓度,并探讨其在大鼠体内吸收、分布及排泄研究。方法:SD大鼠灌胃给予毛蕊花糖苷20,40,80,160 mg·kg^-1后,于不同时间点采血,给予40 mg·kg^-1剂量进行分布和排泄试验,测定血浆、组织和排泄物中的毛蕊花糖苷浓度,并用DAS 2.0软件拟合并计算药动学参数。结果:大鼠给药20,40,80,160 mg·kg^-1的毛蕊花糖苷后,药时曲线呈二室开放模型,主要药动学参数t_max,C_max,t_1/2α,AUC_0-t,AUC_0-∞,CL/F,V/F分别为(17.50±10.37)min、(0.313±0.04)mg·L^-1、(6.79±12.10)min、(21.39±4.03)mg·L^-1·min^-1、(22.39±3.89)mg·L^-1·min^-1、(1.83±0.30)L·min^-1·kg^-1、(179.10±52.77)L·kg^-1。大鼠给予40 mg·kg^-1的毛蕊花糖苷后,毛蕊花糖苷在尿液和粪便中36 h内的累积排泄百分数分别为(0.037±0.005)%、(0.004 2±0.000 8)%,胆汁中12 h内的累积排泄率基本为零。结论:毛蕊花糖苷在大鼠体内吸收符合一级动力学,分布在小肠和肺浓度最高,其次为胃和肌肉,其他组织都有少量的分布;且通过尿液、粪便和胆汁排泄量较少,其可能主要通过代谢过程进行消除。

Absorption,distribution and excretion of acteoside in rats

OBJECTIVE To establish a LC-MS/MS method for determination of acteoside in plasma and tissues of rats and investigate absorption, distribution and excretion of acteoside in rats.METHODS SD rats were given 20, 40, 80 and 160 mg·kg^-1 acteoside ig. Blood samples were collected at different times after oral administration. Concentrations of acteoside in plasma, tissues and excretion were determined by LC-MS/MS, and pharmacokinetics were calculated by DAS 2.0 software.RESULTS After administration of acteoside, concentration-time curve of acteoside was best fitted to a two compartment open model. Main pharmacokinetie parameters t_max, C_max, t_1/2, AUC_0-t, AUC_0-∞, CL/F and V/F were respectively (17.50±10.37)min, (0.313±0.04)mg·L^-1, (6.79±12.10)min, (21.39±4.03)mg·L^-1·min^-1, (22.39±3.89)mg·L^-1·min^-1, (1.83±0.30)L·min^-1·kg^-1 and (179.10±52.77)L·kg^-1. After administration of 40 mg·kg^-1 acteoside, percentage of cumulative excretion were (0.037±0.005)% and (0.004 2±0.000 8)%, respectively in urine and fecal matter of rats thirty six hours later, but zero in bile twelve hours later.CONCLUSION The characters of acteoside are first-order kinetics, intestine and lung are major distribution organs, stomach and muscle rank the second. There are very few acteoside excreted through urine, fecal matter or bile. The major way of elimination is metabolism.