Pharmacokinetic and pharmacodynamic herb-drug interaction of aspirin with Ijintang (Er Chen Tang) or Cheongsanggyeontongtang (Qing Shang Juan Tong Tang): An exploratory study in healthy adults

Ethnopharmacological relevance: Ijintang (IJT) and Cheongsanggyeontongtang (CGT) are traditional herbal medicines frequently administered to post-stroke patients in the Republic of Korea, a population that commonly co-administer them with aspirin for secondary stroke prevention. This concurrent use creates a high potential for clinically significant herb-drug interactions. Aim of the study: This study aimed to evaluate the potential pharmacokinetic (PK) and pharmacodynamic (PD) interactions between aspirin and two herbal formulas, IJT and CGT, in healthy adults. Materials and methods: An open-label, randomized, three-period, two-sequence crossover trial was conducted in 14 healthy volunteers. Participants received a single 100 mg dose of aspirin alone, and then with multiple doses of IJT or CGT. PK parameters of acetylsalicylic acid (ASA) and salicylic acid (SA), and PD effects on serum thromboxane B2 (TXB2) were assessed. Results: Co-administration with IJT showed a non-significant trend towards increased ASA exposure (Geometric LSM ratio [90 % CI] for AUC_last: 1.4362 [0.7547–2.7335]) and decreased SA exposure. Conversely, CGT co-administration showed a trend toward decreased ASA exposure (Geometric LSM ratio for AUC_last: 0.7695 [0.4092–1.4472]). Both herbal medicines enhanced aspirin's antiplatelet effect, evidenced by a significant reduction in the maximum change from baseline (MCFB) of TXB2 compared to aspirin alone. The co-administration was safe and well-tolerated. Conclusions: Co-administration of IJT and CGT with aspirin tended to alter the PK profile of aspirin and enhance its antiplatelet activity. While appearing safe in the short-term, the augmented antiplatelet effect warrants clinical awareness of potential interactions, especially with long-term use.