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牡氧化代谢的影响。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，高蛋白饮食使地西浮t 1/2β缩短，AUC降低，Cls增高;使地西浮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。
Abstract
OBJECTIVE;To determine whether dietary factors play an important role in interindividual variations inoxidative 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.RESULI'S:After a single dose of diazepam(15 mg·kg-1，ip) was given to rats, the half-life ofelimination(t1/2β) 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 dietcompared 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 proteindiet 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
饮食 /
药物氧化代谢 /
美芬妥英
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Key words
diet /
oxidative drug metabolism /
mephenytoin /
diazepam
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参考文献
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