地非三唑与黄酮类化合物的代谢相互作用  

Metabolism-based interaction of diphenytriazol and flavone compounds

作　　者：胡云珍[1] 顾少君[1] 徐亚萍[1] 姚彤炜[1] 

机构地区：[1]浙江大学药学院药物分析和药物代谢研究室

出　　处：《浙江大学学报（医学版）》2008年第2期150-155,共6页Journal of Zhejiang University(Medical Sciences)

基　　金：浙江省中医药管理局科研基金重点项目(2006Z016)

摘　　要：目的:研究地非三唑与黄酮类化合物槲皮素、山奈酚、异鼠李素和四方蒿提取物的代谢相互作用。方法:选取山奈酚、异鼠李素和四方蒿提取物作为二相代谢葡醛酸结合反应的底物,分别在空白、β-萘黄酮和地非三唑诱导的微粒体中进行体外二相代谢,采用HPLC法测定各底物的剩余量。选取槲皮素、山奈酚对地非三唑体外一相代谢进行抑制试验,采用HPLC法测定地非三唑的剩余量。结果:地非三唑诱导的鼠肝微粒体对山奈酚、异鼠李素和四方蒿提取物的二相代谢均强于BNF诱导的鼠肝微粒体(P<0.01)。槲皮素或山奈酚对地非三唑的一相代谢有较强抑制作用,抑制常数分别为(12.41±0.26)μg.m-l 1和(7.97±0.08)μg.m-l 1。结论:地非三唑与上述黄酮类化合物在体外会发生代谢性药物相互作用。Objective： To observe the metabolism-based interaction of diphenytriazol and flavone compounds. Methods： Flavone compounds kaempferol, isoharmnten and Elsholtzia blanda benth extract were chosen as the substrate of glucuronidation in the phase Ⅱ metabolism. The metabolism was investigated in different rat liver microsome incubates pretreated with β -naphthoflavone （BNF）, diphenytriazol and tea oil （control）. The concentrations of residual substrate were determined by HPLC. Quercetin and kaempferol were coincubated with diphenytriazol in control microsome to evaluate the inhibition for phase Ⅰ metabolism. The concentration of diphenytriazol was determined by HPLC. Results： The phase Ⅱmetabolic activity of kaempferol,isoharmnten and Elsholtzia blanda benth extract in diphenytriazol-treated microsome was more potent than that in BNF-treated microsome （P〈0. 01）. The phase I metabolism of diphenytriazol was markedly inhibited by quercetin and kaempferol, with the inhibition constants （Ki） （12. 41±0. 26）μg · ml^-1 and （7. 97±0.08）μg ·ml ^-1,respectively. Conclusion： Diphenytriazol demonstrates metabolism-based interaction with flavone compounds in vitro.

关 键 词：三唑类 蒿属/化学 地非三唑 槲皮素 山奈酚 异鼠李素 四方蒿 代谢相互作用 

分 类 号：R96[医药卫生—药理学]