甘草和五味子对大鼠丙咪嗪药代动力学的影响

以丙咪嗪为探针药物,采用体内代谢的方法研究甘草和五味子对大鼠肝微粒体细胞色素P450(CYP450)的影响。将大鼠随机分为甘草、五味子、生理盐水(空白对照)、苯巴比妥(阳性对照)组,测定各组CYP450的质量摩尔浓度。并于末次给药次日,进行大鼠右侧颈静脉插管手术。手术后第2天静脉给予丙咪嗪,定点取血,HPLC法测定丙咪嗪体内代谢变化。结果:各中草药组CYP450的水平均被显著诱导,丙咪嗪的体内代谢发生了明显改变。研究显示甘草和五味子对大鼠CYP450有诱导作用,且与剂量及诱导时间有关;被诱导的大鼠丙咪嗪的体内代谢加快,甘草和五味子与丙咪嗪合用时药代动力学发生改变。

Effects of Glycyrrhiza Uralensis Fisch and Schisandra Chinensis Baill on Cytochrome P450 in Rats

To identify the effect on the rat hepatic CYP450 content after administer Glycyrrhiza uralensis Fisch and Schisandra chinensis Baill and to assay of substrates enzyme content an NADPH-generating system consisting of imipramine metabolic in vivo was conducted. Rats were randomly divided into groups. The studied animals were allowed free access to water but the drug was given at morning blank abdomen. Two groups of rats received different dose of schisandra chinensis Baill or glycyrrhiza uralensis Fisch plant extracts once daily orally for three or six days. For rats in other groups received once dailly orally normal saline as blank control group and phenobarbital as positive control group at the same time The cytochrome P450 content of the groups of rats receiving schisandra chinensis Baill or glycyrrhiza uralensis Fisch plant extracts was enhanced; the pharmacokinetics of imipramine was changed. It is suggested that Glycyrrhiza uralensis Fisch and Schisandra chinensis Baill are inducer of the CYP450. The CYP450 content is relative with the time and dose of the traditional Chinese medcine. The metabolism of imipramine is quickened, and the pharmacokinetics of imipramine is changed.