多索茶碱对大鼠肝CYP2D6酶的影响  

Effect of Doxofylline on Rat Liver CYP2D6 Enzyme Activity

作　　者：黄丽军[1,2] 于卫江[3] 刘艳[1] 余辉艳 朱大岭[1,2] 

机构地区：[1]哈尔滨医科大学附属第二医院临床药学药物研究所,哈尔滨市150086 [2]黑龙江省高校重点实验室,哈尔滨市150086 [3]河南省肿瘤医院药剂科,郑州市450008

出　　处：《中国药房》2008年第34期2656-2658,共3页China Pharmacy

基　　金：黑龙江省自然科学基金重点资助项目(ZJY03-8)

摘　　要：目的:通过体内、体外实验观察多索茶碱对大鼠肝CYP2D6酶的影响。方法:取16只大鼠随机均分为对照Ⅰ组和实验组,分别灌胃给予生理盐水1mL和多索茶碱50mg·kg-1·d-1,连续1周,第8天时均灌胃给予探针药物右美沙芬(6mg·kg-1),收集8h尿液后处死大鼠,测定大鼠尿样及肝微粒体中右美沙芬浓度并计算其代谢率;实验组肝微粒体再分为对照Ⅱ组、多索茶碱组和CYP2D6特异性抑制剂西咪替丁组,分别加入相应药物孵育后测定并计算右美沙芬的代谢率;将体内、体外实验得到的右美沙芬的代谢率进行相关性分析。结果:以右美沙芬的代谢率为指标,体内实验中2组比较无明显差别(P>0.05);体外试验中,与对照Ⅱ组比较,多索茶碱组未见明显降低(P>0.05),西咪替丁组明显降低(P<0.01);体内和体外实验数据具有很好的相关性(r=0.9537)。结论:多索茶碱对大鼠肝CYP2D6酶无诱导或抑制作用。OBJECTIVE ： To investigate the effects of doxofylline on rat liver CYP2D6 enzyme activity in vivo and in vitro respectively. METHODS： A total of 16 rats were randomly assigned to intragastrically receive normal saline 1 mL （control group I , n ： 8） or doxofylline （50 mg·kg^-1 . d^-1） （trial group, n ： 8） for 1 week. All rats were intragastrically administered with dextromethorphan （DM, 6 mg · kg^-1） on day 8, with rats＇ urine sample within 8 h collected, then the rats were sacrificed. The concentrations of DM in urine sample and liver microsomes were determined to calculate the metabolism rate of DM. The trial group was subdivided into control group Ⅱ , doxofylline group and cimetidine （CYP2D6 specific inhibitor） group. After incubation with the corresponding drugs, the metabolism rates of DM were computed. Then a correlation analysis was performed for the metabolism rates of DM obtained from the in vivo and in vitro experiments. RESULTS： The in vivo test showed no significant difference in DM metabolic rate between the trial group and the control group Ⅰ （P〉0.05）. In the in vitro test, compared with control group Ⅱ , no significant decrease in DM metabolic rate was noted for doxofylline group （P 0.05）, but the DM metabolic rate was significantly reduced in cimitidine group （P（0.01） . There were good correlation between the in vivo and in vitro experimental data （r = 0.953 7） . CONCLUSIONS： Doxofylline showed no ability to induce or inhibit CYP2D6 enzyme in rat liver.

关 键 词：多索茶碱 CYP2D6酶 大鼠 右美沙芬 西咪替丁 肝微粒体 

分 类 号：R974[医药卫生—药品] R965[医药卫生—药学]