丹参
药代动力学
药理学
生物利用度
体内
化学
迷迭香酸
医学
生物化学
中医药
抗氧化剂
生物
病理
生物技术
替代医学
作者
L. Tong,Junling Yang,Xiumei Gao,Ping Chen,Feifei Du,Yan Sun,Fengqing Wang,Fang Xu,Hongcai Shang,Yühong Huang,Yi Wang,R. Wan,Changxiao Liu,Boli Zhang,Chuan Li
标识
DOI:10.1124/dmd.108.021592
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.
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