探针药物评价藤黄酸对肝细胞色素P450酶亚型的影响

Application of Probe Drugs for Detecting Influences of Gambogic Acid on Cytochrome P450 Isoforms

目的用Cocktail探针药物法,研究藤黄酸对大鼠肝细胞色素P450(CYP450)的影响。方法将SD大鼠随机分组,藤黄酸组给予藤黄酸0.5%CMC-Na溶液(2mg·mL-1),以0.5%CMC-Na为空白对照,在一定的时间点采集血样,通过HPLC检测探针药物在大鼠体内的代谢情况,以评价藤黄酸对肝细胞色素P450酶的影响。结果藤黄酸组中咖啡因和氨苯砜的代谢情况与空白组没有显著性差异,但氯唑沙宗的代谢加快,t1/2缩短。结论藤黄酸对代谢酶CYP1A2及CYP3A4的影响不明显,但对代谢酶CYP2E1具有诱导作用。

Objective To research the influences of gambogic acid on rats＇ cytochrome P450 isoforms by using the Cocktail probe drugs. Methods Rats were randomly divided into several groups. One group of rats received gambogic acid solution containing 0. 5 % CMC - Na （2 mg · mL^-1, once per day） orally for six days. At the same time, the rats in the other group received 0. 5 % CMC - Na solution serving as blank control group. Blood samples were collect at different time point, and the plasma concentration of cocktail probe drugs was determined by HPLC. Results There was insignificant difference of caffeine and dapsone metabolism between the gambogic acid group and the blank group, but the chlorzoxazone was eliminated faster in the gambogic acid group, and the half life of chlozoxazone was shorter. Conclusion Gambogic acid has no significant influence on the eytochrome P450 isoforms of CYP1A2 and CYP3A4, but has an induction on the CYP2E1.