Interaction of Clopidogrel and Fufang Danshen Dripping Pills Assay in Coronary Heart Disease based on Non-target Metabolomics.

Ethnopharmacological relevance: Clopidogrel is the recommended treatment by current clinical practice guidelines to prevent adverse cardiovascular events in patients with coronary heart disease (CHD), but this treatment regimen still fails and 5-40% patients display inadequate antiplatelet responses. Fufang Danshen Dripping Pill (FDDP), a Chinese patient drug, was used as the combination with clopidogrel to improve the therapeutic effect. However, the mechanism of the interaction between clopidogrel and FDDP has not been elucidated. Materials and methods: We have used non-targeted metabolism method based on GC-MS and LC-MS for the investigation of drug interactions between clopidogrel and FDDP. 63 patients were divided into four groups with different dosage regimen and the serum samples were collected for the analysis. Results: We have found 5 and 55 differential metabolites between health volunteer group and CHD patients group, respectively. The contents of these differential metabolites had diverse changes in clopidogrel group, FDDP group, and drug combination group, indicating that the clopidogrel and FDDP combination can adjust the glycometabolism, lipid metabolism, and phospholipid metabolism, sequentially made the content of downstream related metabolites towards to the health volunteer group. Conclusion: This work has explained the mechanism of the interaction between clopidogrel and FDDP from the point of view of metabolic product change, and revealed the potential metabolic pathways it affects, which provided the new ideas for clinical medication.