大鼠肝微粒体体外代谢奥美拉唑的研究  

IN VITRO STUDIES ON OMEPRAZOLE METABOLISM IN RAT LIVER MICROSOMES

作　　者：赵莉[1] 楼雅卿[1] 

机构地区：[1]北京医科大学药理系

出　　处：《药学学报》1995年第4期248-253,共6页Acta Pharmaceutica Sinica

摘　　要：建立了大鼠肝微粒体体外孵育代谢奥美拉唑酶促反应及用反相ＨＰＬＣ法测定奥美拉唑两种主要代谢物——羟基奥美拉唑和奥美拉唑砜含量的方法．吉果表明，奥美拉唑主要通过羟化和Ｓ原子氧化反应进行代谢。其羟化反应的最大反应速率为２０３３ｎｍｏｌ／（ｍｉｎ·ｍｇｐｒｏｔｅｉｎ），米氏常数为４６．８ｕｍｏｌ·Ｌ－１，而Ｓ原子氧化反应的最大反应速率为１８７．９ｎｍｏｌ／（ｍｉｎ·ｍｇｐｒｏｔｅｉｎ），米氏常数为１２０．７Ｕｍｏｌ·Ｌ－１。同时证明，美芬妥英、５种苯二氮类药物及罂粟碱对奥美拉唑的羟化代谢均有显著的抑制作用，其中罂粟碱的作用最强。The matabolism of omeprazole to its two major metabolites,hydroxyonicprazolc(OH- OPZ )and omeprazole sulfone(OPZ-SFN )was studied in rat liver microsomcs by a reversedphase HPLC assay.The formation of metabolites of OPZ depcnded on incubation time,siibstrateconcentration,rnicrosomal protein concentration,and was found to be optimal at pH4.The vmaxand Km of OPZ hydroxylation in the rat liver microsomal preparation were 2033 nmol/(min.mgprotein) and 46.8μmol·L- respectively.The maximum rate of formation of OPZ-SFN( VMAX )was 187.9 nmol/(min·mg protein),with a Km value of l20.7μmol·L-1in rat liver microsome,Moreover,the effects of 7 drugs on OPZ metabolism were tested。The resuIts showed thatmephenytoin,benzodiazepines(DZ,NDZ,TMZ,FNZ,NZ)and papaverine caused inhibition ofOPZ metabolism,among them papaverine was the only fairly strong inhibitor.

关 键 词：奥美拉唑 大鼠 肝微粒体 动物实验 药理 

分 类 号：R975.6[医药卫生—药品]