Pharmacokinetics of Valerenic Acid in Rats after Intravenous and Oral Administrations
Pharmacokinetics of Valerenic Acid in Rats after Intravenous and Oral Administrations
复制标题
DOI：
10.1055/s-0031-1298301
复制
发表时间：
2012-04-01
期刊：
影响因子：
2.7
通讯作者：
Butterweck, Veronika
中科院分区：
文献类型：
--
作者：
Sampath, Chethan;Haug, Karin;Butterweck, Veronika
缬草酸（Valerenic acid， VA）是一种倍半萜类化合物，是缬草主要的次生生物活性代谢物之一。迄今为止，关于VA的体内吸收、生物利用度、处置和代谢的研究还很有限。我们建立并验证了一种测定大鼠血浆中VA的LC-MS/MS方法，并成功地将该方法用于大鼠静脉注射和口服给药后的药代动力学研究。采用WinNonlin软件对血浆浓度-时间数据进行非区室法和区室法分析。静脉给药后，VA在大鼠血浆中的分布呈两期，分为快速分布期和缓慢消除期。分布相的半衰期为6-12 min，终端消除相的半衰期为6-46 h，表明可能存在较大的组织结合。口服治疗后戊酸的处置PK也用清除率（CL/F）为2-5 L的双室模型描述。h(1)。kg（-1）和体积分布（V-d） 17- 20l。公斤(1)。口服给药后的吸收程度(F)估计为33.70%，半衰期为2.7-5 h。剂量和auc方面观察到剂量比例，表明在大鼠所研究的剂量水平下呈线性药代动力学。
Valerenic acid (VA), a sesquiterpenoid, is one of the major secondary bioactive metabolites of Valeriana officinalis L. Until now in vivo studies on the absorption, bioavailability, disposition, and metabolism of VA are limited. We established and validated an LC-MS/MS assay for the determination of VA in rat plasma and successfully used this method for pharmacokinetic studies in rats after intravenous (i.v.) and oral administrations. The plasma concentration-time data was analyzed by both non-compartmental and compartmental approaches using WinNonlin software. Following i.v. administration, the disposition of VA in rat plasma was biphasic, subdivided into a fast distribution and a slow elimination phase. The half-life of the distribution phase was 6-12 min, and that of the terminal elimination phase 6-46 h, indicating a possible large tissue binding. Disposition PK of valerenic acid after oral treatment was also described by a two-compartment model with a clearance (CL/F) of 2-5 L . h(-1) . kg(-1) and volume of distribution of (V-d) 17-20 L . kg(-1). The extent of absorption (F) after oral administration was estimated to be 33.70% with a half-life of 2.7-5 h. Dose proportionality was observed in terms of dose and AUCs, suggesting linear pharmacokinetics at the dose levels studied in rats.