Pharmacokinetics, tissue distribution, metabolism, and excretion of depside salts from Salvia miltiorrhiza in rats
Pharmacokinetics, tissue distribution, metabolism, and excretion of depside salts from Salvia miltiorrhiza in rats
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DOI：
10.1124/dmd.106.013045
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发表时间：
2007-02-01
影响因子：
3.9
通讯作者：
Wang, Yiping
中科院分区：
文献类型：
--
作者：
Li, Xiaochuan;Yu, Chen;Wang, Yiping
丹参是一种传统中药材，被称为“丹参”，广泛应用于临床，具有活血化瘀、治疗冠心病的作用。丹参缩酚盐是一种以紫草酸镁B及其类似物为活性成分的新型药物。通过液相色谱-串联质谱法研究了 Sprague-Dawley 大鼠静脉注射后三种主要成分紫精酸 B、迷迭香酸 (RA) 和紫精酸 (LA) 的药代动力学、组织分布、代谢和排泄。当给予 60 mg/kg 丹参缩酚酸盐时，LSB、RA 和 LA 的消除半衰期分别为 1.04、0.75 和 2.0 h。 LSB、RA 和 LA 的曲线下面积分别为 51.6、6.6 和 25.2 mg center dot h/l，各个组织中的值按以下顺序递减：LSB 的肾 > 肺 > 肝 > 心 > 脾 > 脑； RA 的肾 > 肺 > 心 > 肝 > 脾 > 脑；对于 LA，心脏 > 肺 > 肾 > 肝 > 脾 > 脑。静脉注射60 mg/kg丹参缩酚酸盐后，6 h内86%的LSB从胆汁中排出。血清中发现主要代谢物M1和M2。总体而言，结果表明丹参的缩酚酸盐在大鼠静脉内给药后迅速而广泛地分布到组织中，但它们也被快速清除和排泄。
Salviae miltiorrhiza, a traditional Chinese medical herb known as "Danshen," has been widely used in clinics to improve blood circulation, relieve blood stasis, and treat coronary heart disease. Depside salts from S. miltiorrhiza are a novel drug in which magnesium lithospermate B and its analogs are the active components. The pharmacokinetics, tissue distribution, metabolism, and excretion of three of the major components, lithospermic acid B, rosmarinic acid ( RA), and lithospermic acid ( LA), were studied by liquid chromatography-tandem mass spectrometry following intravenous administration in Sprague-Dawley rats. The elimination half-lives for LSB, RA, and LA were 1.04, 0.75, and 2.0 h, respectively, when 60 mg/kg S. miltiorrhiza depside salts were administrated. The areas under the curve for LSB, RA, and LA were 51.6, 6.6, and 25.2 mg center dot h/l, respectively, and the values decreased in the individual tissues in the following order: kidney > lung > liver > heart > spleen > brain for LSB; kidney > lung > heart > liver > spleen > brain for RA; and heart > lung > kidney > liver > spleen > brain for LA. After intravenous administration of 60 mg/kg S. miltiorrhiza depside salts, 86% of the LSB was excreted in the bile within 6 h. The main metabolites M1 and M2 were found in the serum. Overall, the results show that depside salts from S. miltiorrhiza are rapidly and widely distributed to tissues after intravenous administration in rats but that they are also rapidly cleared and excreted.