β-eudesmol 是苍术 (AL) 的主要生物活性成分。 AL 已被开发为标准化 AL 提取物的胶囊制剂，用于治疗胆管癌 (CCA)。然而，草药产品的复杂成分增加了不良药物相互作用的风险。前期研究表明β-eudesmol对rCYP2C19和rCYP3A4有抑制作用。本研究旨在鉴定负责β-桉醇代谢的细胞色素P450（CYP）亚型，并确定微粒体系统中β-桉醇代谢的酶动力学参数和代谢稳定性。使用人重组 CYP (rCYP) 和 CYP1A2、CYP2C9、CYP2C19、CYP2D6 和 CYP3A4 的选择性化学抑制剂进行反应表型分析，并使用人肝微粒体 (HLM) 研究酶动力学和代谢稳定性。结果表明 CYP2C19 和 CYP3A4 在 β-eudesmol 代谢中发挥重要作用。 β-桉树醇的消失半衰期（t1/2）和内在清除率（CLint）分别为17.09分钟和0.20毫升/分钟·毫克蛋白质。酶动力学分析显示蛋白质的米氏常数（Km）和最大速度（Vmax）分别为16.76μM和3.35nmol/min·mg。作为 AL 的一种成分，β-桉醇作为 CYP2C19 和 CYP3A4 的底物和抑制剂，当 AL 与其他草药或常规药物共同给药时，具有很高的药物相互作用潜力。© 2023 作者。药理研究

β-eudesmol is a major bioactive component of Atractylodes lancea (AL). AL has been developed as the capsule formulation of standardized AL extract for treating cholangiocarcinoma (CCA). However, the complex constituents of herbal products increase the risk of adverse drug interactions. β-eudesmol has demonstrated inhibitory effects on rCYP2C19 and rCYP3A4 in the previous research. This study aimed to identify the cytochrome P450 (CYP) isoforms responsible for the metabolism of β-eudesmol and determine the enzyme kinetic parameters and the metabolic stability of β-eudesmol metabolism in the microsomal system. Reaction phenotyping using human recombinant CYPs (rCYPs) and selective chemical inhibitors of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 was performed, and enzyme kinetics and metabolic stability were investigated using human liver microsome (HLM). The results suggest that CYP2C19 and CYP3A4 play significant roles in β-eudesmol metabolism. The disappearance half-life (t1/2 ) and intrinsic clearance (CLint ) of β-eudesmol were 17.09 min and 0.20 mL/min·mg protein, respectively. Enzyme kinetic analysis revealed the Michaelis-Menten constant (Km ) and maximum velocity (Vmax ) of 16.76 μM and 3.35 nmol/min·mg protein, respectively. As a component of AL, β-eudesmol, as a substrate and inhibitor of CYP2C19 and CYP3A4, has a high potential for drug-drug interactions when AL is co-administered with other herbs or conventional medicines.© 2023 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.