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

中国临床药理学与治疗学 ›› 2011, Vol. 16 ›› Issue (12): 1397-1401.

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

严非, 夏春华, 熊玉卿

南昌大学医学院临床药理研究所,南昌 330006,江西

收稿日期:2011-06-22 修回日期:2011-10-31 出版日期:2011-12-26 发布日期:2012-01-07
通讯作者: 熊玉卿,通信作者,女,教授,博士生导师,研究方向:临床药理学与药物代谢动力学。Tel: 0791-6360654 E-mail: xiongyuqing2009@hotmail.com
作者简介:严非,男,硕士研究生,研究方向:临床药理学。Tel: 15107989167 E-mail: yanfei19870915@163.com
基金资助:
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)

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

YAN Fei, XIA Chun-hua, XIONG Yu-qing

Clinical Pharmacology Institute of Nanchang University, Nanchang 330006, Jiangxi, China

Received:2011-06-22 Revised:2011-10-31 Online:2011-12-26 Published:2012-01-07

摘要/Abstract

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AUC_LPZ/AUC_{5-OH LPZ}比值(AUC_lansoprazole/AUC_{5-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 30 mg 兰索拉唑后,发现突变型个体AUC_0-t、AUC_0-∞、CLz、(AUC_LPZ/AUC_{5-OH LPZ})_0-t、(AUC_LPZ/AUC_{5-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。

关键词: CYP2C19, 基因多态性, 兰索拉唑, 药代动力学

Abstract: AIM: To investigate the effect of CYP2C19 polymorphism on pharmacokinetic characteristics and 5-hydroxyl metabolic pathway of lansoprazole in Chinese subjects.METHODS: Twelve healthy subjects were typed by using RFLP-PCR method. After intravenous drip 30 mg lansoprazole, the plasma concentrations of lansoprazole in subjects were determined by LC-MS method. The pharmacokinetic parameters of lansoprazole and AUC_LPZ/AUC_{5-OH LPZ} were calculated and compared between different groups.RESULTS: After all the subjects were given 30 mg lansoprazole, it found that the AUC_0-t, AUC_0-∞, CLz, (AUC_LPZ/AUC_5-OH)_0-t and (AUC_LPZ/AUC_5-OH)_0-∞ of the mutant types were equivalent to 2.381, 2.572, 0.428, 3.602 and 4.083-fold 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 5-hydroxyl metabolic pathway of the lansoprazole (P<0.01). The result suggests that CYP2C19 genetic polymorphism is one of the important factors leading to individual concentration differences of the lansoprazole and has a better relevance with the 5-hydroxyl metabolic pathway.

Key words: CYP2C19, Polymorphism, Lansoprazole, Pharmacokinetics

中图分类号:

R969

严非, 夏春华, 熊玉卿. 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[J]. 中国临床药理学与治疗学, 2011, 16(12): 1397-1401.

YAN Fei, XIA Chun-hua, XIONG Yu-qing. Effect of CYP2C19 genetic polymorphism on pharmacokinetic characterstics and 5 - hydroxyl metabolic pathway of lansoprazole in Chinese volunteers[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(12): 1397-1401.

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