Drug-drug interactions between salvianolate injection and aspirin based on their metabolic enzymes

Abstract

BackgroundIt is unclear whether the combination of traditional Chinese medicine and Western medicine leads to interactions in pharmacokinetics (PKs) and pharmacodynamics (PDs). In this study, the influence of salvianolate and aspirin on metabolic enzymes, and the relationship between the blood concentration and pharmacodynamic indexes, were determined. MethodIn this, randomized, parallel-grouped, single-center clinical trial, 18 patients with coronary heart disease were randomly allocated into three groups: aspirin (AP) group, salvianolate (SV) group, and combination (A + S) group. All treatment courses lasted for 10 days, and blood samples were acquired before and after administration at different timepoints. The expression of catechol-O-methyltransferase (COMT), CD62p, procaspase-activating compound 1 (PAC-1), P2Y12, phosphodiesterase, and mitogen-activated protein kinase 8 (MAPK8) were compared with variance analysis The blood concentrations were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. ResultsSixteen subjects completed the study. No significant difference in COMT was found among groups, although there was a decrease in the SV group. The PK results indicated that the absorption time of salicylic acid was shortened and the AUC0-∞ decreased and the elimination time of salvianolic acid B was prolonged and the AUC0-∞ decreased. The PD results declined after administration. A significant difference was found in MAPK8, CD62p, and P2Y12 expression. Compared with the SV group, a significant difference in P2Y12 in the A + S group was found. ConclusionA pharmacokinetic drug-drug interaction was found in the aspirin and salvianolate combination. Pharmacodynamically, there was no difference between the A + S and AP groups. However, P2Y12 expression in the combination group was superior to that in the SV group. Trial registration numbersThe trial was registered on October 9, 2017, ClinicalTrials.gov, NCT03306550. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0007D8H&selectaction=Edit&uid=U0003QY8&ts=2&cx=oiuc9g