Abstract

1. Esculetin is the main active ingredient isolated from Artemisia montana (Nakai) Pamp. and Euphorbia lathyris L. The present study investigated the oral bioavailability and pharmacokinetics of esculetin in rats, following intravenous and oral administration.

2. Twenty Sprague-Dawley rats were randomly assigned to receive 10 mg/kg of esculetin either by the intravenous or oral route. Plasma concentrations of esculetin were measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated using non-compartmental analysis as well as a compartmental modelling approach using WinNonlin^TM and ADAPT 5 software, respectively.

3. According to non-compartmental analysis, the mean oral bioavailability of esculetin was 19%. Mean ± standard deviation values of esculetin half-life, steady-state volume of distribution and clearance, following intravenous dosing, were 2.08 ± 0.46 h, 1.81 ± 0.52 L/kg and 1.27 ± 0.26 L/h/kg, respectively. As indicated by compartmental modelling, a two-compartment pharmacokinetic model with first-order absorption and elimination rate constants of 0.98 ± 0.18 h⁻¹ and 2.47 ± 0.28 h⁻¹, respectively, sufficiently described the plasma concentration–time curve of esculetin.

4. Improving our understanding of the pharmacokinetic properties of esculetin could help with future development of herbal medicine products with appropriate bioactivity.

摘要

1. Esculetin 是从Artemisia montana (Nakai) Pamp 中分离出来的主要活性成分。和Euphorbia lathyris L。本研究调查了大鼠静脉和口服给药后七叶亭的口服生物利用度和药代动力学。

2. 20 只 Sprague-Dawley 大鼠被随机分配接受 10 mg/kg 的七叶树素，通过静脉内或口服途径。使用液相色谱-串联质谱法测量七叶亭素的血浆浓度。分别使用非房室分析和房室建模方法使用 WinNonlin ^TM和 ADAPT 5 软件估计药代动力学参数。

3. 根据非房室分析，七叶亭的平均口服生物利用度为 19%。静脉给药后七叶亭半衰期、稳态分布容积和清除率的平均值 ± 标准偏差值分别为 2.08 ± 0.46 h、1.81 ± 0.52 L/kg 和 1.27 ± 0.26 L/h/kg。如室模型所示，一级吸收和消除速率常数分别为 0.98 ± 0.18 h ^-1和 2.47 ± 0.28 h ^-1的二室药代动力学模型充分描述了七叶亭的血浆浓度-时间曲线。

4. 提高我们对七叶亭药代动力学特性的理解有助于未来开发具有适当生物活性的草药产品。