Dong Rui-Hua, Fang Zhong-Ze, Zhu Liang-Liang, Ge Guang-Bo, Cao Yun-Feng, Li Xiao-Bao, Hu Cui-Min, Yang Ling, Liu Ze-Yuan
Department of Clinical Pharmacology, Affiliated Hospital, Academy of Military Medical Sciences, Beijing, China.
Pharmazie. 2012 Dec;67(12):1002-6.
Carvacrol and thymol are phenolic compounds with similar structures isolated from many aromatic plants, and have been demonstrated to exert multiple pharmacological effects. The metabolic and pharmacokinetic behaviour of thymol and carvacrol has received much attention. Carvacrol and thymol have been demonstrated to undergo phase I metabolism such as hydroxylation reaction. However, drug-metabolizing enzymes involved in this process remain unclear. Given that cytochrome P450s (CYPs) are involved in most phase I metabolism, the aim of the present study was to investigate the role of CYPs in the metabolism of thymol and carvacrol. After incubation with human liver microsomes (HLMs) in the presence of NADPH, a new metabolite and two metabolites were detected for thymol and carvacrol, respectively. A combination of chemical inhibition studies and assays with recombinant CYP isoforms demonstrated that CYP2A6 was the predominant drug-metabolizing enzyme involved in the metabolism of thymol and carvacrol. All these results remind the researchers that special attention should be paid on pharmacokinetic and clinical outcomes when thymol or carvacrol was co-administrated with other compounds mainly undergoing CYP2A6-mediated metabolism.
香芹酚和百里香酚是从许多芳香植物中分离出的结构相似的酚类化合物，并已被证明具有多种药理作用。百里香酚和香芹酚的代谢和药代动力学行为受到了广泛关注。香芹酚和百里香酚已被证明会经历I相代谢，如羟基化反应。然而，参与这一过程的药物代谢酶仍不清楚。鉴于细胞色素P450（CYPs）参与了大多数I相代谢，本研究的目的是探讨CYPs在百里香酚和香芹酚代谢中的作用。在存在NADPH的情况下与人肝微粒体（HLMs）孵育后，分别检测到百里香酚的一种新代谢物和香芹酚的两种代谢物。化学抑制研究和重组CYP同工酶测定相结合表明，CYP2A6是参与百里香酚和香芹酚代谢的主要药物代谢酶。所有这些结果提醒研究人员，当百里香酚或香芹酚与其他主要通过CYP2A6介导代谢的化合物合用时，应特别关注药代动力学和临床结果。
