银杏内酯B对CYP2C9底物双氯芬酸在大鼠体内药动学和药效学的影响  

Effects of ginkgolide B on the pharmacokinetics and pharmacodynamics of diclofenac,a substrate of cytochrome P450 2C9,in rats

作　　者：汪电雷[1] 刘李[1] 邓远雄[1] 刘海燕[1] 谢林[1] 刘晓东[1] 王广基[1] 

机构地区：[1]中国药科大学药物代谢与动力学研究中心

出　　处：《中国新药杂志》2008年第11期919-922,926,共5页Chinese Journal of New Drugs

基　　金：国家高技术研究发展计划资助项目(2003AA2Z347A);江苏省药物代谢与动力学重点实验室资助项目(BM2001201)

摘　　要：目的:在大鼠体内,以双氯芬酸为工具药,研究银杏内酯B对双氯芬酸药动学和药效学的影响,阐明银杏内酯B对大鼠肝细胞色素P450 2C9(CYP 2C9)是否有抑制或诱导作用。方法:通过观察大鼠连续给予银杏内酯B(剂量为12 mg·kg^(-1),ip,bid,连续7 d)前后对单次给予临床等效量的双氯芬酸(15 mg·kg^(-1),iv)的药时曲线及药动学参数的改变,评价其对双氯芬酸药动学的影响,并评价银杏内酯B连续给药后对单次给予双氯芬酸抗足跖肿胀作用药效学的影响。结果:连续给予银杏内酯B后,与用药前比较,双氯芬酸及其主要代谢物4-羟基双氯芬酸的血药浓度及其药动学参数未见显著性改变;双氯芬酸抗足跖肿胀作用亦未见显著性改变。结论:多剂量给予银杏内酯B对临床等效量双氯芬酸在大鼠体内药动学和药效学无显著影响;银杏内酯B对大鼠肝CYP 2C9无明显的抑制或诱导作用。Objective： To investigate the effects of ginkgolide B （GB）, an important constituent of the leaves of Ginkgo biloba L. , on the pharmacokinetics and pharmacodynamics of diclofenac, a substrate of cytochrome P450 2C9 （CYP 2C9）, in rats. Methods： In a randomized study, healthy rats were pretreated with a recommended dose of GB （ 12 mg·kg-1 , ip, bid） for 7 days; then were iv injected with a single dose of diclofenac （15 mg·kg-1）. After administration of the diclofenac, the inhibition percentages of carragenin-induced edema in hind paws were determined, and the concentrations of diclofenac and 4-hydroxydiclofenac in plasma were meas- ured. Results： After GB treatment, the pharmacokinetic parameters of diclofenac and its main metabolite （4- hydroxydiclofenac） were not affected, and the inhibition of carragenin-induced edema in hind paws by diclofenac were not affected as well. Conclusions： GB at the recommended dose does not affect the pharmacokinetic parameters and the effect of diclofenac in rats, indicating no remarkable influence on CYP 2C9 activity.

关 键 词：银杏内酯B 细胞色素P450 2C9(CYP 2C9) 双氯芬酸 药动学 药效学 

分 类 号：R285.5[医药卫生—中药学] R969.2[医药卫生—中医学]