力达霉素的体外代谢  

Lidamycin metabolism in vitro

作　　者：温艳清[1] 孟志云[1] 陈淑珍[2] 朱晓霞[1] 窦桂芳[1] 

机构地区：[1]军事医学科学院野战输血研究所,北京100850 [2]中国医学科学院中国协和医科大学医药生物技术研究所,北京100050

出　　处：《药学学报》2011年第9期1132-1136,共5页Acta Pharmaceutica Sinica

基　　金：国家新药创制重大专项资助项目(2009ZX909304-004);"重大新药创制"科技重大专项("十一五"计划)资助项目(2008ZX09101-013)

摘　　要：旨在研究力达霉素在血浆和肝微粒体中的体外代谢性质,指导临床合理用药。选择HPLC-MS/MS测定方法,通过测定力达霉素的活性成分,考察力达霉素在大鼠、比格犬、猕猴和人血浆及肝微粒体中的代谢稳定性以及在人肝微粒体中对细胞色素P450(cytochrome P450,CYP450)各亚型酶的抑制作用。结果表明,力达霉素在4个种属血浆中均有代谢,其代谢速率为大鼠>比格犬>人>猕猴;在4个种属肝微粒体中,只有在猕猴肝微粒体中代谢;在浓度为0.000 5～10 ng·mL-1时,对人肝微粒体中细胞色素P450各亚型酶几乎无抑制作用。可见力达霉素在人体内的代谢性质与比格犬体内较相似,而且临床上当力达霉素与通过CYP450酶代谢的药物合用时,不会导致这些药物的代谢减慢。This paper is to report the study of the metabolism of lidamycin in vitro including in plasma and microsomes to guide clinical therapy.Lidamycin was quantified by detecting its active ingredient using HPLC-MS/MS.The metabolic stability of lidamycin in rat,Beagle dog,monkey and human plasma and liver microsomes,and its inhibition to cytochrome P450 isoforms in human liver microsomes were studied.Results showed that lidamycin was metabolized in the four species of plasma,and the sequence of metabolic rates in plasma were in rat in dog in human in monkey.But among the four species of liver microsomes,lidamycin was metabolized only in monkey liver microsomes.There was almost no inhibition to cytochrome P450 isoforms at the concentrations of between 0.000 5 and 10 ng·mL 1.Therefore,the property of lidamycin metabolism in human is similar with that in dog,and metabolism of other drugs would not be decreased by cytochrome P450 as used along with lidamycin in clinic.

关 键 词：力达霉素 体外代谢 肝微粒体 

分 类 号：R969[医药卫生—药理学]