Systemic Exposure to and Disposition of Catechols Derived from Salvia miltiorrhiza Roots (Danshen) after Intravenous Dosing DanHong Injection in Human Subjects, Rats, and Dogs
文献类型：期刊论文
| 作者 | Li, Meijuan4,5; Wang, Fengqing4; Huang, Yuhong2; Du, Feifei4; Zhong, Chenchun4; Olaleye, Olajide E.4; Jia, Weiwei4; Li, Yanfen2; Xu, Fang4; Dong, Jiajia4 |
| 刊名 | DRUG METABOLISM AND DISPOSITION
 |
| 出版日期 | 2015-05 |
| 卷号 | 43期号:5页码:679-690 |
| ISSN号 | 0090-9556 |
| DOI | 10.1124/dmd.114.061473 |
| 文献子类 | Article |
| 英文摘要 | DanHong injection is a Danshen (Salvia miltiorrhiza roots)-based injectable solution for treatment of coronary artery disease and ischemic stroke. Danshen catechols are believed to be responsible for the injection's therapeutic effects. This study aimed to characterize systemic exposure to and elimination of Danshen catechols in human subjects, rats, and dogs receiving intravenous DanHong injection. A total of 28 catechols were detected, with content levels of 0.002-7.066 mM in the injection, and the major compounds included tanshinol, protocatechuic aldehyde, salvianolic acid B, rosmarinic acid, salvianolic acids A and D, and lithospermic acid with their daily doses >= 10 mu mol/subject. After dosing, tanshinol, salvianolic acid D, and lithospermic acid exhibited considerable exposure in human subjects and rats. However, only tanshinol had considerable exposure in dogs. The considerable exposure to tanshinol was due to its having the highest dose, whereas that to salvianolic acid D and lithospermic acid was due to their relatively long elimination half-lives in the human subjects and rats. Protocatechuic aldehyde and rosmarinic acid circulated in the bloodstream predominantly as metabolites; salvianolic acids A and B exhibited low plasma levels with their human plasma metabolites little or not detected. Tanshinol and salvianolic acid D were eliminated mainly via renal excretion. Elimination of other catechols involved hepatobiliary and/or renal excretion of their metabolites. Methylation was found to be the primary metabolism for most Danshen catechols and showed intercompound and interspecies differences in rate and degree in vitro. The information gained here is relevant to pharmacological and toxicological research on DanHong injection. |
| WOS关键词 | TANDEM MASS-SPECTROMETRY ; DIODE-ARRAY DETECTION ; LIQUID-CHROMATOGRAPHY ; ENDOTHELIAL DYSFUNCTION ; PROTOCATECHUIC ALDEHYDE ; PARKINSONS-DISEASE ; HOMOCYSTEINE ; EXTRACT ; ACID ; PHARMACOKINETICS |
| 资助项目 | National Science Fund of China for Distinguished Young Scholars[30925044] ; National Science and Technology Major Project of China "Key New Drug Creation and Manufacturing Program"[2009ZX09304-002] ; National Science and Technology Major Project of China "Key New Drug Creation and Manufacturing Program"[2013ZX09201020001003] ; National Basic Research Program of China[2012CB518403] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000352002800004 |
| 出版者 | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276563]  |
| 专题 | 上海药物代谢研究中心 科研与新药推进处 |
| 通讯作者 | Li, Chuan |
| 作者单位 | 1.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing, Peoples R China 2.Tianjin Univ Tradit Chinese Med, Affiliated Hosp 2, Tianjin, Peoples R China; 3.Buchang Pharm Grp, Xian, Shaanxi Provinc, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 5.Univ Chinese Acad Sci, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Meijuan,Wang, Fengqing,Huang, Yuhong,et al. Systemic Exposure to and Disposition of Catechols Derived from Salvia miltiorrhiza Roots (Danshen) after Intravenous Dosing DanHong Injection in Human Subjects, Rats, and Dogs[J]. DRUG METABOLISM AND DISPOSITION,2015,43(5):679-690. |
| APA | Li, Meijuan.,Wang, Fengqing.,Huang, Yuhong.,Du, Feifei.,Zhong, Chenchun.,...&Li, Chuan.(2015).Systemic Exposure to and Disposition of Catechols Derived from Salvia miltiorrhiza Roots (Danshen) after Intravenous Dosing DanHong Injection in Human Subjects, Rats, and Dogs.DRUG METABOLISM AND DISPOSITION,43(5),679-690. |
| MLA | Li, Meijuan,et al."Systemic Exposure to and Disposition of Catechols Derived from Salvia miltiorrhiza Roots (Danshen) after Intravenous Dosing DanHong Injection in Human Subjects, Rats, and Dogs".DRUG METABOLISM AND DISPOSITION 43.5(2015):679-690. |
入库方式： OAI收割
来源：上海药物研究所
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