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Drug Metabolism and Disposition Fast Forward
First published on November 28, 2006; DOI: 10.1124/dmd.106.013045

0090-9556/07/3502-234-239$20.00
DMD 35:234-239, 2007

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Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Depside Salts from Salvia miltiorrhiza in Rats

Xiaochuan Li, Chen Yu, Youli Lu, Yunlong Gu, Jie Lu, Wei Xu, Lijiang Xuan, and Yiping Wang

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China (X.L., Y.L., Y.G., J.L., W.X., L.X., Y.W.); and Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China (C.Y.)

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 · 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.

Address correspondence to: Prof. Yiping Wang, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. E-mail: ypwang{at}mail.shcnc.ac.cn






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