The pharmacokinetics and oral bioavailability studies of columbianetin in rats after oral and intravenous administration
The pharmacokinetics and oral bioavailability studies of columbianetin in rats after oral and intravenous administration
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DOI：
10.1016/j.jep.2013.08.030
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发表时间：
2013-10-28
影响因子：
5.4
通讯作者：
Chang, Yan-xu
中科院分区：
文献类型：
--
作者：
Luo, Qian;Wang, Chun-peng;Chang, Yan-xu
民族药理学相关性：当归的根。我国自古以来就有治疗风湿性疾病的传统中药，但其作用机制尚不清楚。Columbianastrin是从RAP中分离得到的主要活性成分之一，已被证明具有多种生物活性，但其体内吸收特性和口服生物利用度的剂量比例性研究尚未见报道。雄性Sprague道利大鼠（210-230 g）接受静脉注射（i. v. 5、10和20 mg kg（-1））或口服（5、10和20 mg kg（-1））剂量的Columbianlavin。采用反相高效液相色谱法（HPLC）测定血浆中的哥仑比安时。样品前处理采用乙酸乙酯液液萃取法。结果：色谱柱为Cm柱，以水-甲醇为移动的流动相，流速为1 mL min（-1）。在0.05 ~ 2000 μ g/mL范围内，线性关系良好。大鼠血浆样品中哥仑比星的日内和日间准确度均在8%以内，变异小于8.3%。该方法适用于大鼠静脉给药和口服给药后血浆中哥仑比安时的测定和药代动力学研究。结果表明，在口服给药后0.3-0.5 h，达到了Columbianastrin的最大血浆浓度（Cm）（17-42 μ g mL（-1）），表观分布容积（V/F）范围为0.38 - 0.44 L。哥伦比亚噻托溴铵的绝对生物利用度分别为81.13 +/- 45.85、81.09 +/- 33.63和5430 +/-23.19%。经口给药后的终末消除半衰期（T-1/2）为60-90 min，是静脉给药的2.5 ~ 33倍。结论：大鼠口服Columbianastrin后的药代动力学特征为口服吸收快、清除快、绝对生物利用度好。5、10和20 mg/kg口服剂量的Columbianastrin的生物利用度范围为54 - 81%。Columbianastrin的生物利用度与研究的剂量无关。在5-20 mg/kg（-1）的剂量范围内，Columbianvide显示出剂量比例性。这一结果表明，哥伦比亚豆是RAP的物质基础之一。本研究为中药研究提供了一种高效液相色谱分析方法。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: The roots of Angelica pubescens Maxim. f biserrata Shan et Yuan (RAP) has been used as Traditional Chinese medicine to treat rheumatic disease in China since ancient times, but its action mechanisms was not well understood. Columbianetin is one of the main active constituents isolated from RAP, which has been shown to have various biological activities, but the absorption characteristics and oral bioavailability dose proportionality of columbianetin in vivo were not studied.Materials and methods: Male Sprague Dawley rats (210-230 g) received either an intravenous (i.v. 5, 10 and 20 mg kg(-1)) or oral (5, 10 and 20 mg kg(-1)) dose of columbianetin. The levels of columbianetin in plasma were measured by a simple and sensitive reversed-phase high-performance liquid chromatography (HPLC) method. The simple liquid-liquid extraction with ethyl acetate was used for sample preparation. Osthole was selected as internal standard (IS).Results: The chromatographic separation was accomplished on a Cm column at a flow rate of 1 mL min(-1), where water-methanol was used as mobile phase. The calibration curve of the method was linear in the concentration range of 0.05-2000 mu g mL(-1). The intra and inter-day accuracy for columbianetin in rat plasma samples were within 8% and the variation was less than 8.3%. This method was suitable for the determination and pharmacokinetic study of columbianetin in rat plasma after both intravenous and oral administration. The results indicated that maximum plasma concentrations(Cm) for the columbianetin (17-42 mu g mL(-1)) were achieved at 0.3-0.5 h post-oral dosing and the apparent volume of distribution (V/F) ranged from 038 to 0.44 L. Absolute bioavailability of columbianetin was assessed to be 81.13 +/- 45.85, 81.09 +/- 33.63 and 5430 +/- 23.19%, respectively. Terminal elimination half-life (T-1/2) of the columbianetin after oral dosing was 60-90 min and were 2.5-33 fold longer than those observed for the i.v. dosing.Conclusions: The pharmacokinetic properties of columbianetin in rat after oral administration were characterized as rapid oral absorption, quick clearance and good absolute bioavailability. The bioavailability of columbianetin ranged from 54 to 81% for 5,10 and 20 mg kg(-1) oral doses. The bioavailability of columbianetin is independent of the doses studied. Columbianetin showed dose proportionality over the dose range 5-20 mg kg(-1). The results clearly demonstrated that columbianetin was one of the material bases of RAP. Furthermore, an HPLC method was demonstrated in this study for the research of traditional Chinese medicine. (C) 2013 Elsevier Ireland Ltd. All rights reserved.