摘要
目的:研究银杏叶制剂对辛伐他汀体外代谢及其代谢相关酶的影响,探讨两药是否存在相互作用,为临床上两药的合理联用提供试验依据。方法:将大鼠随机分为4组:分别为生理盐水对照组、苯巴比妥钠阳性对照组、低剂量银杏叶制剂组和高剂量银杏叶制剂组。灌胃10天后,处死动物摘取肝脏并制备成微粒体。分光光度法测定各组微粒体蛋白含量,红霉素N-脱甲基酶(ERDase)活性,HPLC测定辛伐他汀体外代谢情况。结果:与生理盐水对照组比较:苯巴比妥钠阳性对照组微粒体蛋白含量、ERDase活性及辛伐他汀体外代谢均显著增加(P<0.05);高剂量银杏叶组上述各指标也明显增加(P<0.05),且数值均介于生理盐水和苯巴比妥钠两组之间;低剂量银杏叶组各指标仅有增加趋势,但差别无统计学意义。结论:大剂量银杏叶制剂可以诱导CYP3A的活性,促进辛伐他汀的体外代谢,提示银杏叶制剂与辛伐他汀或其他CYP3A底物合用时要注意药物的相互作用。
Objective： To conclude the possible interaction between gingko extract and simvastatin, by studing the effect of gingko extract on vitro metabolism of simvastatin and involving critical metabolic enzyme, which can guide the clinicians to use them rationally （propose good guideline for rational using of the two medcine mentioned above）. Method： Thirty-two female SD rats were randomly separated into 4 groups, including negative control group. High dose of gingko extract. Low dose of gingko extractand positive control group. All groups were administered for 10 days with stomach tube, and then the quantity of liver microsome protein, the activity of CYP3A were determined by spectrophotograph, simvastatin was incubated with the liver microsome, and the effect of gingko extract on its metabolism was estimated by measuring the amount of simvastatin by HPLC. Result： Comparing with the negative contrast group：the quantity of liver microsome protein, the activity of CYP3A and the metabolism of simvastatin in positive control group were all increased markly （P 〈 0. 05）. In high dose group, the quantity of liver microsome protein and the activity of CYP3A were both increased significantly （P 〈 0. 05）, and the metabolism of simvastatin also accelerate obviously （P 〈 0. 05）. But in the low dose group significant distinction of every index was not found. Conclusion： High dose of gingko extract can induce the activity of CYP3A, and promote the metabolism of simvastatin, so the medical interaction should be focused when gingko extract is coadministered with simvastatin and other substracts of CYP3A.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2009年第12期1578-1581,共4页
China Journal of Chinese Materia Medica
作者简介
[通信作者]李方洁，主任医师，主要研究心脏电生理。Tel：（010）84739035，E-mail：WJXD2007@yahoo．com；
通信作者 梁日欣，研究员，主要研究药代动力学。Tel：（010）64014411-2948，E-mail：Rxliang@
