Plasma and urinary tanshinol from Salvia miltiorrhiza (Danshen) can be used as pharmacokinetic markers for cardiotonic pills, a cardiovascular herbal medicine

doi:10.1124/dmd.108.021592

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 上海药物代谢研究中心

	Plasma and urinary tanshinol from Salvia miltiorrhiza (Danshen) can be used as pharmacokinetic markers for cardiotonic pills, a cardiovascular herbal medicine
	Lu, Tong 2; Yang, Junling; Gao, Xiumei 4; Chen, Ping ; Du, Feifei ; Sun, Yan ; Wang, Fengqing ; Xu, Fang ; Shang, Hongcai 4; Huang, Yuhong 4
刊名	DRUG METABOLISM AND DISPOSITION
	2008-08
卷号	36 期号:8 页码:1578-1586
ISSN号	0090-9556
DOI	10.1124/dmd.108.021592
文献子类	Article
英文摘要	Cardiotonic pills are a type of cardiovascular herbal medicine. To identify suitable pharmacokinetic (PK) marker(s) for indicating systemic exposure to cardiotonic pills, we examined the in vivo PK properties of putatively active phenolic acids from the component herb Danshen (Radix Salviae miltiorrhizae). We also performed in vitro and in silico assessments of permeability and solubility. Several phenolic acids were investigated, including tanshinol (TSL); protocatechuic aldehyde (PCA); salvianolic acids A, B, and D; rosmarinic acid; and lithospermic acid. Plasma TSL exhibited the appropriate PK properties in dogs, including dose-dependent systemic exposure in area under concentration-time curve (AUC) and a 0.5-h elimination half-life. In rats, more than 60% of i.v. TSL was excreted intact into the urine. In humans, we found a significant correlation between the urinary recovery of TSL and its plasma AUC. The absorption rate and bioavailability of TSL were not significantly different whether cardiotonic pills were given p.o. or sublingually. The gender specificity in plasma AUC disappeared after body-weight normalization, but the renal excretion of TSL was significantly greater in women than in men. PCA was predicted to be highly permeable according to in vitro and in silico studies; however, extensive presystemic hepatic elimination and degradation in the erythrocytes led to extremely low plasma levels and poor dose proportionality. Integrated in vivo, in vitro, and in silico studies on the other phenolic acids showed poor gut permeability and nearly undetectable levels in plasma and urine. In conclusion, plasma and urinary TSL are promising PK markers for cardiotonic pills at the tested dose levels.
WOS关键词	ROSMARINIC ACID ; PROTOCATECHUIC ALDEHYDE ; MASS-SPECTROMETRY ; AQUEOUS EXTRACT ; RAT ; METABOLISM ; BIOAVAILABILITY ; PERMEABILITY ; ABSORPTION ; HUMANS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
WOS记录号	WOS:000257829900018
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272849]
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.Tianjin Inst Pharmaceut Res, Tianjin State Key Lab Pharmacodynam & Pharmacokin, Tianjin, Peoples R China 2.Chinese Acad Sci, Grad Sch, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Ctr DMPK Res, SIBS, Shanghai 201203, Peoples R China; 4.Tianjin Univ Tradit Chinese Med, Tianjin, Peoples R China;
推荐引用方式 GB/T 7714	Lu, Tong,Yang, Junling,Gao, Xiumei,et al. Plasma and urinary tanshinol from Salvia miltiorrhiza (Danshen) can be used as pharmacokinetic markers for cardiotonic pills, a cardiovascular herbal medicine[J]. DRUG METABOLISM AND DISPOSITION,2008,36(8):1578-1586.
APA	Lu, Tong.,Yang, Junling.,Gao, Xiumei.,Chen, Ping.,Du, Feifei.,...&Li, Chuan.(2008).Plasma and urinary tanshinol from Salvia miltiorrhiza (Danshen) can be used as pharmacokinetic markers for cardiotonic pills, a cardiovascular herbal medicine.DRUG METABOLISM AND DISPOSITION,36(8),1578-1586.
MLA	Lu, Tong,et al."Plasma and urinary tanshinol from Salvia miltiorrhiza (Danshen) can be used as pharmacokinetic markers for cardiotonic pills, a cardiovascular herbal medicine".DRUG METABOLISM AND DISPOSITION 36.8(2008):1578-1586.