Bioavailability and pharmacokinetics of alantolactone from Inula helenium in rats following intravenous and oral administrations  

土木香内酯在大鼠体内的生物利用度及药物动力学研究（英文）

作　　者：张新国[1] 刘琎文 寇飞[1] 王强林[1] 刘子裕[1] 李建勇 

机构地区：[1]兰州理工大学生命科学与工程学院甘肃省中藏药筛选评价及深加工重点实验室,甘肃兰州730050 [2]中国农科院兰州畜牧与兽药研究所农业部兽用药物创制重点实验室/甘肃省新兽药工程重点实验室,甘肃兰州730050

出　　处：《Journal of Chinese Pharmaceutical Sciences》2017年第4期284-290,共7页中国药学（英文版）

基　　金：The National Natural Science fund of China(Grant No.31360379);the open fund of the Key Laboratory of the New Animal Drug Project of Gansu Province;the Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture(Grant No.2014)

摘　　要：Alantolactone, as the principal constituent oflnula Helenium L, has been shown various pharmacologic activities, such as anti-inflammatory and deworming. In the present study, we developed a high performance liquid chromatography （HPLC） method for the determination of alantolactone in rat plasma, and pharmacokinetics of alantolactone was investigated after intravenous and oral administrations to Wistar rats. Separation was achieved on C18 column （4.6 mm×250 mm, 5.0 μm） using a mobile phase consisting of methanol-water （70：30, v/v） at a flow rate of 1.0 mL/min. The wavelength of the ultraviolet detector was set at 239 nm. The excellent linearity was found over a concentration range of 0.08-10 μg/mL （R2 = 0.9998）. The intra- and inter-day precisions were good, and the RSD was lower than 2.27%. The mean absolute recovery of alantolactone in plasma ranged from 88.09% to 95.57%. After intravenous administration, alantolactone showed rapid systemic clearance （CL （0.11±0.014） L/h/kg） and small volume of distribution （Vd （0.71±0.14） L/kg）. The biological half life （t1/2） was 56.24 min. After oral administration, alantolactone showed rapid oral absorption in rats, with a short Tmax of （45.02±0.88） and （45.13±0.39） min for 14 and 28 mg/kg, respectively. The bioavailability of alantolactone in rats was 50.88%, indicating that alantolactone was orally available.土木香内酯是藏药土木香中挥发油的主要成分,具有较好的驱虫、抗炎等药理活性。本研究以高效液相色谱(HPLC)方法测定大鼠血浆中的土木香内酯含量,评价静脉和口服给予大鼠土木香内酯的药代动力学特征。研究采用C18柱(4.6 mm×250 mm,5.0μm),以甲醇–水(70:30,v/v)为流动相,流速1.0 m L/min的进行分离,检测波长为239 nm。结果发现土木香内酯在0.08–10μg/m L的浓度范围,具有良好的线性关系(R^2=0.9998),且日内和日间精密度RSD均低于2.27%,血浆中土木香内酯的平均绝对回收率为88.09%–95.57%。静脉给药后,土木香内酯显示了较快的清除(CL=(0.11±0.014)L/h/kg)和较小分布(Vd=(0.71±0.14)L/kg),消除半衰期(t_(1/2))为56.24 min。口服14和28 mg/kg的剂量后,土木香内酯在大鼠中显示了较快的吸收,Tmax分别为(45.02±0.88)min和(45.13±0.39)min。进一步的分析显示,大鼠口服土木香后土木香内酯的生物利用度为50.88%,提示具有土木香药材中土木香内酯具有较好的吸收。

关 键 词：HPLC ALANTOLACTONE PHARMACOKINETIC BIOAVAILABILITY 

分 类 号：R285.5[医药卫生—中药学]