Evaluation of herb-drug interactions between compound Danshen Dripping Pills and clopidogrel based on the pharmacokinetics and pharmacodynamics in rats.

Compound Danshen Dripping Pills (CDDP), a well-known traditional Chinese medicine, is widely used to prevent and treat cardiovascular diseases. CDDP is usually prescribed in combination with clopidogrel (CLP), but the herb-drug interactions are rarely reported. This study evaluated the effects of CDDP on the pharmacokinetics and pharmacodynamics of co-administered CLP, and ensured the safety and efficacy of their usage. The trial design included a single-dose administration and multi-dose test for seven consecutive days. Wistar rats received CLP alone or CLP combined with CDDP. After the final dose, plasma samples were collected at various time points, and the active metabolite H4 of CLP was analyzed by UFLC-MS/MS. The main pharmacokinetic parameters of C , T , t , AUC and AUC were calculated using the non-compartment model. Additionally, prothrombin time, activated partial thromboplastin time, bleeding time and adenosine diphosphate-induced platelet aggregation were evaluated for anticoagulation and anti-platelet aggregation activity. In this study, we found that CDDP had no significant effect on the metabolism of CLP in rats. In pharmacodynamic studies, the combination group showed significant synergistic antiplatelet activity compared to the CLP or CDDP groups alone. Based on pharmacokinetic and pharmacodynamic results, CDDP and CLP have synergistic effects on anti-platelet aggregation and anticoagulation.