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学科主题: 物理化学
题名: Identification of CYP isoforms involved in metabolism of corynoline and assessment of CYP-mediated drug-drug interaction
作者: Fang ZZ(房中则) ;  Yang L(杨凌)
会议名称: 18th International Symposium on Microsomes and Drug Oxidations
会议日期: 2010-5-16
出版日期: 2010-05-16
会议地点: 中国
通讯作者: Ling Yang
部门归属: 十八室
主办者: Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College
摘要: Corynoline, an isoquinoline alkaloid isolated from the genus Corydalis, has been demonstrated to show multiple pharmacological effects including inhibition of acetylcholinesterase, inhibition of cell adhesion, fungitoxic and cytotoxic activity (Kim, 2002; Kamigauchi et al., 2005). Although much attention has been focused on its pharmacological study, information on the metabolism of corynoline and CYP inhibitory potential still remains unclear. The present study focused on its metabolism and metabolism-based drug-herb interactions. After corynoline was incubated with human liver microsomes (HLMs) in the presence of NADPH, two demethylenated metabolites (M-1 and M-2) were formed. Chemical inhibition experiment and assays with recombinant CYP isoforms showed CYP2C9 was mainly involved in the formation of M-1 and CYP3A4 mainly catalyzed the production of M-2. Among seven major CYP isoforms tested, corynoline showed strong inhibitory effects on the activities of CYP3A4 and CYP2C9, with an IC50 of 3.3±0.9 μM and 31.5±0.5 μM, respectively. Kinetic analysis showed that inhibition of CYP3A4 by corynoline was best fit to a noncompetitive manner with Ki of 3.2 μM, while inhibition of CYP2C9 by corynoline was best fit to a competitive manner with Ki of 6.3 μM. Additionally, corynoline exhibited time-dependent inhibition (TDI) to CYP3A4. The inactivation kinetic parameters (KI and kinact) were calculated to be 6.8 μM and 0.07 min-1, respectively. These data are helpful for the clinical application of corynoline and corynoline-containing herbs.
语种: 中文
内容类型: 会议论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/114060
Appears in Collections:中国科学院大连化学物理研究所_会议论文

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Recommended Citation:
Fang ZZ,Yang L. Identification of CYP isoforms involved in metabolism of corynoline and assessment of CYP-mediated drug-drug interaction[C]. 见:18th International Symposium on Microsomes and Drug Oxidations. 中国. 2010-5-16.
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