五味子和甘草对大鼠肝药酶的诱导作用导致利多卡因药动学的改变

首都医科大学学报 ›› 2005, Vol. 26 ›› Issue (1): 43-43.

五味子和甘草对大鼠肝药酶的诱导作用导致利多卡因药动学的改变

唐静成, 张锦楠, 李亚伟

首都医科大学化学生物学与药学院

收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2005-02-24 发布日期:2005-02-24
通讯作者: 张锦楠

Evaluation of Enzyme Induction Effect of Schisandra Chinensis and Glycyrrhiza Uralensis on Pharmacokinetics of Lidocaine in Rats

Tang Jingcheng, Zhang Jinnan, Li Yawei

School of Chemical Biology and Pharmaceutical Sciences, Capital University of Medical Sciences

Received:1900-01-01 Revised:1900-01-01 Online:2005-02-24 Published:2005-02-24

摘要/Abstract

摘要：

过大鼠的体外和体内药代动力学研究, 探讨了五味子和甘草与其他药物之间的相互作用。雄性SD大鼠口服6d五味子或甘草水煎液, 剂量为生药1g或3g/kg, 空白对照和阳性对照分别给予蒸馏水和苯巴比妥钠(0.12g/kg), 制备各给药组肝微粒体并测定P₄₅₀水平。以利多卡因为探针药物, 以给予五味子、甘草或苯巴比妥钠6d的大鼠肝微粒体研究其体外代谢速率;在体内药代动力学的研究中, 大鼠先口服6d五味子、甘草或苯巴比妥钠, 第7天静脉给予利多卡因(10mg/kg), 测定血浆和尿液中利多卡因的浓度, 计算出药动学参数。结果:五味子组和甘草组大鼠P₄₅₀水的平与对照相比有显著差异, P₄₅₀水平与剂量和时间呈相关性。第6天, 与空白对照的P₄₅₀水平(0.695μmol/g)相比, 五味子组、甘草组和苯巴比妥钠组分别增加了58%、91%和270%。在服用了五味子、甘草和苯巴比妥钠的大鼠肝微粒体中利多卡因的代谢速率明显高于空白对照, 而体内的药动学参数也明显改变。在五味子组和甘草组中, 利多卡因的半衰期分别缩短了28%和39%, 总清除率增加了76%和59%。表明五味子和甘草对P₄₅₀同工酶具有诱导作用。因此, 当其他药物与五味子或甘草合用时, 其有效性和安全性将会受到影响。

Abstract:

Drug-drug interaction potentials of two herbal medicines, namely Schisandra chi nensis and Glycyrrhiza uralensis, were investigated in rats via in-vitro and in-vivo pharmacokinetic studies.Male SD rats received Schisandra or Glycyrrhiza decoction once daily for 6 days at doses equivalent to 1g or 3 g/kg. Rats receiving distil wat er and Phenobarbital (0.12 g/kg) were used as non-treatment and positive contro ls, respectively. The liver was collected for the preparation of microsomes, and P₄₅₀ levels were measured for different treatment groups. In a separate s tudy, lidocaine was employed as probe compound, and its metabolic rate in the liver mi crosomes prepared from the rats pretreated by Schisandra or Glycyrrhiza or Pheno barbital for 6 days was examined. In the in-vivo pharmacokinetic study, rats we re pretreated with Schisandra or Glycyrrhiza for 6 days. Lidocaine was administ ered on day 7 intravenously at 10 mg/kg dose. Pharmacokinetic parameters of lido caine in plasma and urine were estimated.P₄₅₀ levels in the rats pretreated by Schisandra or Glycyrrhiza were signi ficant higher than that in the non-treatment control. The increase in P₄₅₀ was dose-dependent and time-dependent. On day 6, Schisandra, Glycyrrhiza and Phen obarbital increased P₄₅₀ levels by 58%, 91% and 270% compared to the non-treatm ent control (0.695 μmol/g protein). Metabolic rate of lidocaine in the live r mi crosomes was significantly higher in rats that received Schisandra, Glycyrrhiza or Phenobarbital pretreatment when compared to the non-treatment control. Pharm acokinetic profile of lidocaine was significantly modified in the rats with the herbal pretreatment. Elimination half-lives were shorten by 28% and 39%, and to tal clearances were increased by 76% and 59% in the Schisandra and Glycyrrhiza g roups, respectively.In conclusion, Schisandra and Glycyrrhiza showed induction effect on P₄₅₀ isozymes. Efficacy and safety profiles of a drug may be affected when the herbal products or herbal prescriptions containing these two plant medicines were conc omitantly used.

唐静成;张锦楠;李亚伟. 五味子和甘草对大鼠肝药酶的诱导作用导致利多卡因药动学的改变[J]. 首都医科大学学报, 2005, 26(1): 43-43.

Tang Jingcheng;Zhang Jinnan;Li Yawei . Evaluation of Enzyme Induction Effect of Schisandra Chinensis and Glycyrrhiza Uralensis on Pharmacokinetics of Lidocaine in Rats[J]. Journal of Capital Medical University, 2005, 26(1): 43-43.