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中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (10): 1143-1147.

• 临床药理学 • 上一篇    下一篇

PXR*1B基因多态性与氨氯地平稳态谷浓度和降压疗效的相关性研究

张桂香1,2, 袁洪1, 阳国平1, 黄志军1   

  1. 1中南大学湘雅三医院临床药理中心, 2湖南省第二人民医院药剂科,长沙 410006,湖南
  • 收稿日期:2010-08-11 修回日期:2010-10-16 发布日期:2020-09-16
  • 通讯作者: 黄志军,男,硕士,研究方向:心血管临床药理学。Tel: 0731-88618339 E-mail: mhzj@163.com
  • 作者简介:张桂香,女,硕士研究生,研究方向:临床药理学和临床药学。Tel: 13574887542 E-mail: duoduo0217@163.com
  • 基金资助:
    国家“重大新药创制”科技重大专项(2009ZX09501-032);863计划(2009AA022703);湖南省卫生厅重点项目(A2007-004)

Correlation study of PXR*1B polymorphisms and steady-state trough concentration and its antihypertensive effect of amlodipine

ZHANG Gui-xiang1,2, YUAN Hong2, YANG Guo-ping2, HUANG Zhi-jun2   

  1. 1Center of Clinical Pharmacology, The 3rd Xiangya Hospital of Central South University, 2Department of Pharmacy, Second People's Hospital of Hunan Province, Changsha 410006, Hunan, China
  • Received:2010-08-11 Revised:2010-10-16 Published:2020-09-16

摘要: 目的: 探讨PXR11193T>C、8055 C>T及PXR*1B(由11193T>C和8055 C>T构成)对轻中度原发性高血压患者服用氨氯地平的稳态谷浓度及其降压疗效的影响。方法: 采用基因测序的方法测定PXR11193T>C、8055C>T基因型。采用PHASE V.2.1对PXR*1B单倍体进行分析。62例轻中度原发性高血压患者进入氨氯地平临床试验。患者每天早上服用5 mg氨氯地平,疗程为8周。测定治疗前、治疗4周和8周后的血压。采集第8周服药前血样,用HPLC-MS/MS方法检测氨氯地平的血药浓度。使用SPSS 13.0软件包比较不同基因型组间氨氯地平的稳态谷浓度及降压疗效的差异。结果: 61例轻中度原发性高血压患者完成了药物试验。氨氯地平的有效率为63.9%。PXR11193T>C、8055 C>T位点及PXR*1B不同基因型组间氨氯地平稳态谷浓度和降压疗效差异无统计学意义(P>0.05)。结论: PXR1193T>C、8055C>T及PXR*1B对原发性高血压患者连续服用氨氯地平的稳态谷浓度及降压疗效无显著影响。

关键词: 孕烷X受体, 基因多态性, 氨氯地平, 浓度, 降压疗效

Abstract: AIM: To investigate the effect of PXR11193T>C,8055 C>T and PXR*1B (contain 11193T>C and 8055C>T) on the steady-state trough concentration and antihypertensive effect of amlodipine in essential hypertension patients. METHODS: Genotyping of PXR11193T>C and 8055 C>T were determined by pyrosequencing sequenator. PXR*1B was analyzed by PHASE V.2.1. 62 essentialhypertension patients rolled the clinical trial. They were treated with amlodipine for 8 weeks, according to once a day, 5 mg per time in every morning. Blood pressure was measured at 0, 4, 8-week. At 8-week the venous blood samples were collected before amlodipine administration. Plasma was used to determined concentration of amlodipine by HPLC-MS/MS. Statistical analyses were performed by the SPSS 13.0 software for Windows. RESULTS: 61 of patients finished the clinical trial and the effective power of amlodipine was 63.9%. There was no significantly difference of the steady-state trough concentration and antihypertensive effect of amlodipine among genotypes of PXR11193T>C,8055 C>T and PXR*1B(P>0.05). CONCLUSION: PXR polymorphisms does not significantly affect the steady-state trough concentration and antihypertensive effect of amlodipine in essential hypertension patients.

Key words: Pregnane X receptor, Gene polymorphism, Amlodipine, Concentration, Antihypertensive

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