当前位置： SCI文献检索 > JOURNAL OF ETHNOPHARMACOLOGY期刊下所有文献 > Is it safe to take Radix Salvia Miltiorrhiza - Radix Pueraria Lobate product with warfarin and aspirin? A pilot study in healthy human subjects.

Is it safe to take Radix Salvia Miltiorrhiza - Radix Pueraria Lobate product with warfarin and aspirin? A pilot study in healthy human subjects.

Abstract：

ETHNOPHARMACOLOGICAL RELEVANCE:Radix Salvia Miltiorrhiza (Danshen) and Radix Pueraria Lobate (Gegen) are officially listed in the Chinese Pharmacopoeia and have long been used together as a Compound Chinese Traditional Medicine (CCTM) for treatment of coronary heart diseases, which are often co-administered with aspirin or warfarin to patients suffering from cardiovascular diseases. AIM OF STUDY:Since significant pharmacokinetic and pharmacodynamic interactions between Danshen-Gegen (DG) formula and aspirin/warfarin have been observed in our previous rat studies, the current study was proposed aiming to further verify such pharmacokinetic and pharmacodynamic interactions in healthy human subjects and explore related mechanisms. MATERIALS AND METHODS:A 5-day, multiple dose, five-session clinical trial has been carried out (n = 14) with 2-week washout periods between sessions, during which the subjects would receive different combinations of the medications. Plasma samples were collected for pharmacokinetic evaluation, and whole blood samples were collected for pharmacodynamic evaluation. In addition, an in-vitro mechanistic study is conducted to investigate the role of danshensu on the anti-thrombotic and anti-platelet aggregation effects of warfarin and aspirin respectively. RESULTS:Significant pharmacokinetic and pharmacodynamic herb-drug interactions were observed in healthy human subjects. pharmacokinetically, co-administration of DG with aspirin or warfarin could lead to a moderately increased AUC0→t of aspirin and a decreased AUC0→t of 7-hydroxyl warfarin respectively. The systemic exposure of danshensu (DSS, the marker component of DG) would be significantly increased after co-administration with warfarin. Pharmacodynamically, a reduction in systemic thromboxane B2 concentration was noticed after administration of DG with aspirin, which could be associated with the increased systemic exposure of aspirin and the synergistic effect of danshensu, aspirin and salicylic acid on cyclooxygenase (COX) inhibition. An offset on the warfarin induced soluble thrombomodulin induction was observed after its co-administration with DG, which could be partially attributed to the COX-2 inhibition effect of danshensu. CONCLUSION:Our results indicated that co-administration of DG with aspirin/warfarin would lead to significant pharmacokinetic and pharmacodynamic herb-drug interactions in healthy human subjects.

journal_name

J Ethnopharmacol

journal_title

Journal of ethnopharmacology

authors

Zhang Y,Yang M,Ho NJ,Mok RY,Zhang Z,Ge B,Leung PC,Fung KP,Lau CBS,Lee VHL,Lin Z,Wong RSM,Zuo Z

doi

10.1016/j.jep.2020.113151

subject

Has Abstract

pub_date

2020-11-15 00:00:00

pages

113151

eissn

0378-8741

issn

1872-7573

pii

S0378-8741(20)33033-6

journal_volume

262

pub_type

杂志文章

在线工具

Is it safe to take Radix Salvia Miltiorrhiza - Radix Pueraria Lobate product with warfarin and aspirin? A pilot study in healthy human subjects.