Abstract
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 μmol/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.
Footnotes
- Received October 1, 2014.
- Accepted February 10, 2015.
This work was supported by the National Science Fund of China for Distinguished Young Scholars [Grant 30925044]; the National Science and Technology Major Project of China “Key New Drug Creation and Manufacturing Program” [Grants 2009ZX09304-002 and 2013ZX09201020001003]; and the National Basic Research Program of China [Grant 2012CB518403].
This work was previously presented as a poster presentation at the following workshop: Li et al. (2014) In vivo chemical profiles and metabolic profiles of phenolic acids after intravenous administration of DanHong injection in different species. 5th Asian Pacific Regional Meeting of ISSX; 2014 May 9–12; Tianjin, China.
Justin B. R. Lim was a visiting student from Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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