“鸡尾酒”探针药物法评价苦参对大鼠CYP450不同亚型体内代谢活性的影响  

Simultaneous evaluation on the influence of Radix Sophora flavescentis on CYP450 isoforms by cocktail probe approach in rats

作　　者：呼自顺[1,2] 徐津 李芹[2] 汪云[2] 刘洁[2] 尹玉清[2] 焦建杰[2] 娄建石[2] 

机构地区：[1]天津市第一中心医院药剂科,天津300192 [2]天津医科大学基础医学院药理学教研室,天津300070 [3]天津医科大学口腔医院,天津300070

出　　处：《中国医院药学杂志》2013年第21期1775-1778,共4页Chinese Journal of Hospital Pharmacy

基　　金：天津市自然科学基金重点项目(编号:09JCZDJC21500);高等学校博士学科点专项科研基金(新教师基金)资助课题(编号:20091202120012)

摘　　要：目的:使用"鸡尾酒"(cocktail)探针药物法研究苦参对大鼠CYP1A2、CYP2C9、CYP2E1和CYP3A4体内代谢活性的影响。方法:将大鼠随机分为4组,空白对照组、实验组、诱导剂组和抑制剂组。实验组大鼠每日灌胃给予苦参溶液100mg·kg-1,空白对照组灌胃给予与实验组体积相同的生理盐水;诱导剂组腹腔注射苯巴比妥注射液50 mg·kg-1;抑制剂组腹腔注射西咪替丁注射液50 mg·kg-1,各组均为每日1次,连续5 d。各组分别于第6天注射"鸡尾酒"探针药物溶液,于给药前及给药后不同时间点取血,使用HPLC检测各探针药物的血药浓度,计算其药动学参数,评价相应的CYP450亚型的体内代谢活性。结果:实验组咖啡因和甲苯磺丁脲的AUC0-t和AUC0-∞明显低于空白对照组和抑制剂组(P<0.05),高于诱导剂组(P<0.05);而CL明显高于空白对照组和抑制剂组(P<0.05),低于诱导剂组(P<0.05)。实验组氯唑沙宗的AUC0-t和AUC0-∞明显低于空白对照组和抑制剂组(P<0.05),CL明显高于空白对照组和抑制剂组(P<0.05);与诱导剂组无显著差异(P>0.05)。咪达唑仑的主要药动学参数与空白对照组比较均没有显著差异(P>0.05)。结论:苦参可诱导大鼠体内CYP1A2和CYP2C9,其诱导强度低于苯巴比妥;苦参可诱导大鼠体内CYP2E1,其诱导强度与苯巴比妥相似;苦参对大鼠CYP3A4体内活性未见显著影响。OBJECTIVE To evaluate the effects of Radix Sophora flavescentis on the metabolic activities of CYP isoforms CYP1A2, CYP2Cg, CYP2EI and CYP3A4 by cocktail probe approach in rats in vivo. METHODS The rats were randomly di- vided into four groups as following： control group, experimental group, induction group and inhibition group. Radix Sophora flavescentis were administered orally for five days at a dose of 100 rag. kg i body weight for experimental group and normal sa- line were administered orally for blank control group at the same volume as experimental group. Sodium phenobarbital and cim etidine injection were administered intraperitoneally for five days at a dose of 50 mg.kg-1 body weight for induction group and inhibition group respectively. On the 6th day, cocktail solution was administered by caudal vein for all rats. The blood samples were collected at a series of time-points before and after administration. The plasma concentrations of the different probe drugs were determined by HPLC with UV detection, and the pharmacokinetic parameters were calculated by DAS 2.0. RESULTS In experimental group, the AUG, , and AUC0∞ of caffeine and tolbutamide significantly decreased than those in control group and inhibition group （P〈0. 05） and significantly increased than those in induction group （P〈0. 05）. Meanwhile, the CLs sig- nificantly increased than that in control group and inhibition group （P〈0.05） and significantly decreased than that in induction group （P〈0. 05）. The AUG0-∞ , and AUG0-∞ of chlorzoxazone in experimental group significantly decreased and the CL signifi- cantly increased than those in control group and inhibition group （P〈0. 05）. There were no significant differences compared with those in induction group （P〈0.05）. There were no significant differences for the pharmacokinetic parameters of midazo- lain between experimental group and control group （P;〉0. 05）. CONCLUSION Radix Sophora/lavescentis can induce the met abolic activities of CYPIA2 and

关 键 词：“鸡尾酒”探针药物法 CYP1A2 CYP2C9 CYP2E1 CYP3A4 苦参 

分 类 号：R285.5[医药卫生—中药学]