P2Y12受体抑制剂在临床上广泛用于预防急性冠状动脉综合征和接受经皮冠状动脉介入治疗患者血栓发生，临床代表药物有噻吩并吡啶类药物氯吡格雷和普拉格雷，在研药物有维卡格雷。噻吩并吡啶类药物在治疗中存在剂量高、个体差异大、肠胃出血副作用等临床缺点；在代谢机制研究方面存在较多问题不明了，如：代谢物结构虽相似但活性差别大，活性代谢物清除机制不清楚，临床给药剂量偏高。在前期研究基础上，我们将基于放射性同位素示踪技术，以[14C]维卡格雷、[14C]氯吡格雷和[14C]H1/H2/H3/H4为研究对象，深入研究活性代谢物H2/H4的生成与清除机制、揭示H3/H4甲基化代谢物在血浆暴露量差异的根本原因，并结合动物实验和肝亚细胞组分探究P2Y12受体抑制剂与巯基甲基转移酶抑制剂联合用药的情况。这些研究结果将提高噻吩并吡啶类的临床用药安全性，减弱或避免药物不良反应，为患者安全用药提供科学依据。

P2Y12 receptor inhibitors were widely used in the treatment of acute coronary syndromes (ACS) in clinic. Representative drugs of P2Y12 receptor inhibitors are thienpyridine antiplatelet agents and first-line medicine are clopidogrel and pragrel; meanwhile vicagrel is undergoing phase Ⅲ clinical trial in China. Thienpyridine antiplatelet agents show the respective disadvantage of inter-individual variability in efficacy, high oral dosage, as well as severe side effect of gastrointestinal bleeding in clinic. Besides, metabolic mechanism was still unclear, such as similar structures of metabolites but showing huge different activity; the clearance mechanism of active metabolite is not clear, clinical dosage is too high to cause side-effect. Therefore, we will focus on [14C]vicargrel, [14C]clopidogrel and [14C]H1/H2/H3/H4, combining with low radiation energy radioisotope tracing technology, to study the generation and clearance mechanism of active metabolite H2/H4; to investigate the reasons for different exposure levels of H3/H4 methylated metabolites in plasma; to evaluate the pharmacodynamics in the case of P2Y12 receptor inhibition in combination with thiol methyltransferase inhibitor in animal experiments or liver subcellular components. These basic researches will significantly help eliminate or avoid adverse drug and provide robust scientific evidences for drug safety in clinical practice.