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

Biomed Pharmacother. 2021 Mar:135:111203. doi: 10.1016/j.biopha.2020.111203. Epub 2021 Jan 3.

Abstract

Background: It 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.

Method: In 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.

Results: Sixteen 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.

Conclusion: A 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 numbers: The 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.

Keywords: Aspirin; Drug-drug interaction; Metabolic enzymes; Salvianolate injection.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aspirin / adverse effects
  • Aspirin / pharmacokinetics*
  • Beijing
  • Biotransformation
  • Catechol O-Methyltransferase / blood
  • Coronary Disease / blood
  • Coronary Disease / diagnosis
  • Coronary Disease / drug therapy*
  • Drug Interactions
  • Drugs, Chinese Herbal / adverse effects
  • Drugs, Chinese Herbal / pharmacokinetics*
  • Female
  • Gastrointestinal Absorption
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Mitogen-Activated Protein Kinase 8 / blood
  • P-Selectin / blood
  • Plant Extracts / adverse effects
  • Plant Extracts / pharmacokinetics*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / pharmacokinetics*
  • Receptors, Purinergic P2Y12 / blood

Substances

  • Drugs, Chinese Herbal
  • P-Selectin
  • P2RY12 protein, human
  • Plant Extracts
  • Platelet Aggregation Inhibitors
  • Receptors, Purinergic P2Y12
  • SELP protein, human
  • salvianolate
  • COMT protein, human
  • Catechol O-Methyltransferase
  • Mitogen-Activated Protein Kinase 8
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT03306550