Comparative studies on pharmacokinetic fates of tetrahydropalmatine enantiomers in different chemical environments in rats.
Comparative studies on pharmacokinetic fates of tetrahydropalmatine enantiomers in different chemical environments in rats.
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DOI：
10.1002/chir.20507
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发表时间：
2008-02
期刊：
影响因子：
2
通讯作者：
Z. Hong;Jian Le;Mei Lin;Guorong Fan;Y. Chai;Xueping Yin;Yu-tian Wu
中科院分区：
文献类型：
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作者：
Z. Hong;Jian Le;Mei Lin;Guorong Fan;Y. Chai;Xueping Yin;Yu-tian Wu
四氢巴马汀（Tetrahydropalmatine， THP）是延胡索和由延胡索和白芷组成的中药元胡白芷（Yuanhu-Baizhi， YB）中的有效成分。本研究的目的是比较外消旋THP （rac-THP）、延胡索提取物和YB提取物在大鼠体内THP对映体的药代动力学特征。分别给三组sd大鼠口服单剂量racc - thp （5 mg kg(-1)）或相当于5 mg kg（-1）的连根和YB提取物。定期采集血样，采用非手性-手性高效液相色谱（HPLC）测定血浆中THP对映体的浓度。给药后大鼠THP的C（max）比（-/+）分别为2.91、1.38和1.19，THP的AUC（0近似无穷大）比（-/+）分别为2.84、1.50和1.35。YB提取物对(+)- thp的平均AUC（0近似无穷大）和C（max）分别为0.652 +/- 0.30 microg h ml（-1）和0.148 +/- 0.09 microg ml(-1)，显著高于racc - thp和连根提取物（P < 0.05）。YB提取物对racc - thp的平均AUC（0近似无穷大）和T（max）分别为1.500 +/- 0.56 μ g / ml（-1）和2.12 +/- 1.1 h，显著高于racc - thp和连根提取物（P < 0.05）。这些结果表明，THP对映体在大鼠体内的药代动力学立体选择性在植物形式给药时降低，而在YB提取物给药时，racc -THP的AUC（0近似无穷大）增加，证实了连根和白芍的配伍相容性。
Tetrahydropalmatine (THP) is the active component in Rhizoma corydalis and the medicine Yuanhu-Baizhi (YB), which consists of Rhizoma corydalis and Radix angelicae dahuricae. The aim of this work was to compare pharmacokinetic features of THP enantiomers in rats dosed with racemic THP (rac-THP), Rhizoma corydalis, or YB extracts. A single dose of rac-THP (5 mg kg(-1)) or extracts of Rhizoma corydalis and YB (both equivalent to 5 mg kg(-1) of rac-THP) was given orally to three groups of Sprague-Dawley rats, respectively. Blood samples were collected periodically and plasma concentrations of THP enantiomers were determined using an achiral-chiral high-performance liquid chromatographic (HPLC) method previously reported, with some modifications. The C(max) ratio (-/+) of THP was 2.91, 1.38, and 1.19, and the AUC(0 approximately infinity) ratio (-/+) of THP was 2.84, 1.50, and 1.35 in rats after dosed with rac-THP, extracts of Rhizoma corydalis and YB, respectively. The mean AUC(0 approximately infinity) and C(max) of (+)-THP dosed with YB extracts were 0.652 +/- 0.30 microg h ml(-1) and 0.148 +/- 0.09 microg ml(-1), significantly higher (P < 0.05) than those dosed with rac-THP and Rhizoma corydalis extracts. The mean AUC(0 approximately infinity) and T(max) of rac-THP dosed with YB extracts were 1.500 +/- 0.56 microg h ml(-1) and 2.12 +/- 1.1 h, significantly higher (P < 0.05) than those dosed with rac-THP or Rhizoma corydalis extracts. These findings suggested the stereoselectivity in pharmacokinetics of THP enantiomers in rats was decreased when dosed in plant form, while the AUC(0 approximately infinity) of rac-THP increased when YB extracts were dosed, confirming the compatibility in drug combination of Rhizoma corydalis and Radix angelicae dahuricae.