高蛋白高脂肪高碳水化合物饲料对大鼠地西泮、美芬妥英代谢影响  

The effect of high protein,high fat,and high carbohydrate diet on diazepam and meohenytion metabolism in rats

作　　者：石磊[1,2] 张远[1,2] 

机构地区：[1]广州军区广州总医院临床药理科 [2]北京医科大学药理系药物代谢研究室

出　　处：《中国药学杂志》1997年第2期83-86,共4页Chinese Pharmaceutical Journal

摘　　要：目的：研究高蛋白、高脂肪、高碳水化合物饲料对大鼠地西泮、美芬妥英的体内代谢，以了解饮食因素对药物氧化代谢的影响。方法：ＨＰＬＣ测定用药后不同时间血浆药物及其代谢产物浓度，用３Ｐ８７程序处理数据，求得药动学参数。结果：与对照组相比，高蛋白饮食使地西泮ｔ１／２β缩短，ＡＵＣ降低，Ｃｌｓ增高；使地西泮的代谢产物去甲地西泮的ＡＵＣ增高；使尿液中Ｓ／Ｒ美芬妥英比值明显降低。结论：高蛋白饮食加快地西泮的去甲基化反应，增强Ｓ美芬妥英羟化代谢。OBJECTIVE:To determine whether dietary factors play an important role in interindividual variations in oxidative drug metabolism.METHOD:HPLC was used for the determination of concentration of diazepam,demethyldiazepam,a metabolite of diazepam,and mephenytoin in plasma of rats.Statistical software's 3P87 was used for the calculation of results.RESULTS:After a single dose of diazepam(15 mg·kg -1 ,ip) was given to rats,the half life of elimination(t 1/2β ) and the area under the plasma concentration time curve(AUC) were decreased respectively and the systemic clearance(Cls) was enhanced,but the AUC of demethyldiazepam was increased in rats fed a high protein diet compared with those in rats fed a control diet.The S/R mephenytoin ratio in urine after a single oral dose of racemic mephenytoin(30 mg·kg -1 ) was reduced significantly(P<0.001) by high protein diet.CONCLUSION:The high protein diet enhanced diazepam demethylation and S mephenytoin hydroxylation in the rat.It is concluded that rates of oxidative drug metabolism can be altered by dietary factors.

关 键 词：美芬妥英 地西泮 代谢 碳水化合物 脂肪 蛋白质 

分 类 号：R971.3[医药卫生—药品]