CYP2C19基因多态性对中国人体内兰索拉唑药代动力学及其5-羟基代谢通路的影响  

Effect of CYP2C19 genetic polymorphism on pharmacokinetic characterstics and 5-hydroxyl metabolic pathway of lansoprazole in Chinese volunteers

作　　者：严非[1] 夏春华[1] 熊玉卿[1] 

机构地区：[1]南昌大学医学院临床药理研究所

出　　处：《中国临床药理学与治疗学》2011年第12期1397-1402,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家十一五科技重大专项(2009ZX09309-003-02);国家十二五科技重大专项(2011ZX09302-007-03)

摘　　要：目的:研究CYP2C19基因多态性对中国人体内兰索拉唑药代动力学及其5-羟基代谢通路的影响。方法:采用RFLP-PCR方法对12名健康受试者进行CYP2C19基因多态性检测,并采用液相色谱-质谱法(LC-MS)检测兰索拉唑体内血药浓度并计算相关的药代动力学参数,比较不同基因型受试者之间主要药代动力学参数以及AUCLPZ/AUC5-OH LPZ比值(AUClansoprazole/AUC5-hydroxy lansoprazole,此参数用以评价5-羟基代谢的标准)的差异。结果:12名健康受试者在给予30mg兰索拉唑后,发现突变型个体AUC0-t、AUC0-∞、CLz、(AUCLPZ/AUC5-OH LPZ)0-t、(AUCLPZ/AUC5-OH LPZ)0-∞分别相当于野生型个体的2.381、2.572、0.428、3.602、4.083倍。结论:CYP2C19的基因多态性对中国人体内兰索拉唑药代动力学过程有显著影响(P<0.05),而对兰索拉唑5-羟基代谢通路有极显著影响(P<0.01),结果提示CYP2C19的基因多态性是导致兰索拉唑体内血药浓度个体差异性的重要因素之一,且与兰索拉唑5-羟基代谢通路之间存在更好的相关性。To investigate the effect of CYP2C19 polymorphism on pharmacokinetic characteristics and 5hydroxyl metabolic path way of lansoprazole in Chinese subjects. METHODS： Twelve healthy subjects were typed by using RFLPPCR method. After intravenous drip 30 mg lansoprazole, the plasma concentrations of lansoprazole in subjects were determined byLCMS method. The pharmacokinetie parameters of lansoprazole and AUC_LPZ/AUC_5-OHLPZ were calculated and compared between different groups. RESULTS. After all the subjects were given 30 mg lansoprazole, it found that the AUC_0-1, AUC_0-∞ CLz, （ AUCLpz / AUG5 OH）_0-∞ and （AUCLpz/AUC5 OH）_0-∞of the mutant types were equivalent to 2. 381, 2. 572, 0. 428, 3. 602 and 4. 083fold as those of the wild types, respectively. CONCLUSION ： The CYP2C19 genetic polymorphism, which has significant influence on the pharmacokinetic characteristics of the lansoprazole in Chinese volunteers （P〈0.05）, has very significant influence on the 5hydroxyl metabolic pathway of the lansoprazole （P〈0.01）. The result suggests that CYP2C19 genetic polymorphism is one of the important factors leading to individual concen tration differences of the lansoprazole and has a better relevance with the 5hydroxyl metabolic pathway.

关 键 词：药代动力学参数 CYP2C19 基因多态性 兰索拉唑 代谢通路 羟基 体内 中国 

分 类 号：R969[医药卫生—药理学]