银杏内酯B注射液对大鼠体内CYP酶活性的影响

Influence of ginkgolide B injection on CYP450 activity in rats

目的:研究银杏内酯B注射液对大鼠细胞色素P450酶(CYP)亚型CYP1A2,CYP3A4和CYP2E1活性的影响,为临床合理用药提供参考。方法:将Wistar大鼠随机分组,给药组静脉推注银杏内酯B注射液10 mg·kg-1,qd,对照组给予相同体积的注射液空白溶媒,均给予7 d。d8各组静脉注射茶碱20 mg·kg-1、氨苯砜10 mg·kg-1和氯唑沙宗20 mg·kg-1混合溶液,于给药后5,10,15,30 min及1,1.5,2,4,8,12,24 h采集血浆样品。用HPLC同时测定3种探针药物的血药浓度,用DAS2.0软件计算药动学参数。结果:同对照组相比,给药组茶碱和氯唑沙宗的主要药动学参数均无显著差异,但氨苯砜的表观分布容积(V1)显著增加(P<0.05),消除半衰期(t1/2β)有明显延长趋势。结论:银杏内酯B注射液对大鼠CYP1A2,CYP2E1活性无显著影响,对大鼠CYP3A4活性可能有抑制作用。

Objective： To investigate the influence of ginkgolide B injection on the activities of the cytochrome P450 （CYP） isoforms CYP1A2, CYP3A4 and CYP2E1 in rats. Methods： Rats were randomly divided into two groups. They were injected with ginkgolide B injection through caudal veins at the single dose of 10 mg·kg^-1 once a day for 7 days, or with the same volume of blank injection solvent （control）. On the eighth day, all rats were intravenously administered with single doses of the cocktail probe drugs, theophylline 20 mg·kg^-1, dapsone 10 mg·kg^-1 and chlorzoxazone 20 mg·kg^-1. Blood samples were collected at 5, 10, 15, 30 rain and 1, 1.5, 2, 4, 8, 12, 24 h, and plasma concentrations of the probe drugs were simultaneously determined by HPLC. DAS 2.0 software was used to calculate their individual pharmacokinetic parameters. Results： Compared with the control group, there was no significant difference in the major pharmacokinetie parameters of theophylline and chlorzoxazone in ginkgolide B group. However, the apparent volume of distribution （ V1 ） of dapsone was significantly increased （P 〈 0.05）, and the elimination half life （tl/2/3） of dapsone had a prolonged trend in ginkgolide B group. Conclusion： Ginkgolide B injection has no significant influence on the cytochrome P450 jsoforms CYP1A2 and CYP2E1, but may inhibit the CYP3A4 in rats.