土木香内酯在大鼠体内的生物利用度及药物动力学研究

doi:10.5246/jcps.2017.04.029

中国药学(英文版) ›› 2017, Vol. 26 ›› Issue (4): 284-290.DOI: 10.5246/jcps.2017.04.029

土木香内酯在大鼠体内的生物利用度及药物动力学研究

张新国^1*, 刘琎文¹, 寇飞¹, 王强林¹, 刘子裕¹, 李建勇^2*

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

收稿日期:2016-12-28 修回日期:2017-01-15 出版日期:2017-04-26 发布日期:2017-02-17
通讯作者: Tel.: +86-0931-2976703, +86-0931-2115290, E-mail: biodrug@163.com, lijy1971@163.com
基金资助:
The National Natural Science fund of China (Grant No. 31360379) and the open fund of the Key Laboratory of the New Animal Drug Project of Gansu Province and the Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture (Grant No. 2014).

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

Xinguo Zhang^1*, Jinweng Liu¹, Fei Kou¹, Qianglin Wang¹, Ziyu Liu¹, Jianyong Li^2*

1. Lanzhou University of Technology, School of Life Science and Engineering, Key Laboratory of Herbal-Tebitan Drug Screening and Deep Processing of Gansu Province, Lanzhou 730050, China
2. Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture, Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China

Received:2016-12-28 Revised:2017-01-15 Online:2017-04-26 Published:2017-02-17
Contact: Tel.: +86-0931-2976703, +86-0931-2115290, E-mail: biodrug@163.com, lijy1971@163.com
Supported by:
The National Natural Science fund of China (Grant No. 31360379) and the open fund of the Key Laboratory of the New Animal Drug Project of Gansu Province and the Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture (Grant No. 2014).

摘要/Abstract

摘要：

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, 5.0 μm),以甲醇–水(70:30, v/v)为流动相,流速1.0 mL/min的进行分离,检测波长为239 nm。结果发现土木香内酯在0.08–10 μg/mL的浓度范围,具有良好的线性关系(R²= 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,T_max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。

Abstract:

Alantolactone, as the principal constituent of Inula 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 (t_1/2) was 56.24 min. After oral administration, alantolactone showed rapid oral absorption in rats, with a short T_max 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.

Key words: HPLC, Alantolactone, Pharmacokinetic, Bioavailability

中图分类号:

R969.1

Supporting:

张新国, 刘琎文, 寇飞, 王强林, 刘子裕, 李建勇. 土木香内酯在大鼠体内的生物利用度及药物动力学研究[J]. 中国药学(英文版), 2017, 26(4): 284-290.

Xinguo Zhang, Jinweng Liu, Fei Kou, Qianglin Wang, Ziyu Liu, Jianyong Li. Bioavailability and pharmacokinetics of alantolactone from Inula helenium in rats following intravenous and oral administrations[J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(4): 284-290.

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土木香内酯在大鼠体内的生物利用度及药物动力学研究

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

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