振源胶囊对细胞色素P_(450)酶CYP1A2、CYP3A4、CYP2E1的影响

目的:研究振源胶囊对细胞色素P450酶CYP1A2、CYP3A4、CYP2E1的影响。方法:用Cocktail探针药物法,将Wistar大鼠随机分组,灌胃给予振源胶囊溶液,以生理盐水组为空白对照,诱导10d,于股动脉插管,注射给予3种探针药物咖啡因、氨苯砜、氯唑沙宗,通过高效液相色谱法检测各探针药物的代谢率来评价各组CYP1A2、CYP3A4、CYP2E1亚型酶的活性;药动学计算采用DAS2.0软件完成。结果:给予振源胶囊的大鼠,咖啡因代谢加快,半衰期缩短;氨苯砜代谢减慢,半衰期延长;氯唑沙宗半衰期与空白对照组比较无显著差异(P>0.05)。结论:振源胶囊对大鼠CYP1A2有诱导作用,对CYP3A4有抑制作用,对CYP2E1的作用不明显。

Effects of Zhenyuan Capsule on Cytochrome P450 Enzymes CYP1A2, CYP3A4 and CYP2E1

OBJECTIVE： To study on the effects of Zhenyuan capsule on cytochrome P450 enzymes CYP1A2, CYP3A4 and CYP2E1. METHODS： Cocktail drugs probe was adopted. Wistar rats were randomly given Zhenyuan capsule solution via i.g. gtt or normal saline for 10 days. After femoral catheterization, the rats were given probe drugs of coffine, dapsone and chlorzoxazone. Metabolic rate of probe drugs were determined by HPLC to evaluate the activity of CYP1A2, CYP3A4 and CYP2E1. Pharmacokinetic parameters were calculated using DAS 2.0 software. RESULTS： The metabolism of caffeine speeded up after receiving Zhenyuan capsules with longer t1/2, but the metabolism of dapsone slowed down with shorter t1/2. The t1/2 of chlorzoxazone in Zhenyuan capsulesgroup was not significantly different from in blank control group（P〉0.05）.CONCLUSION： Zhenyuan capsule tended to be the inducer of CYP1A2 and inhibitor of CYP3A4. But the CYP2E1 is hardly affected.