期刊文献+

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 被引量:3

Correlation study of PXR~* 1B polymorphisms and steady-state trough concentration and its antihypertensive effect of amlodipine
下载PDF
导出
摘要 目的:探讨PXR11193T>C、8055C>T及PXR*1B(由11193T>C和8055C>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PHASEV.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5mg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SPSS13.0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、8055C>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。 AIM:To investigate the effect of PXR11193TC,8055 CT and PXR~*1B(contain 11193TC and 8055CT) on the steady-state trough concentration and antihypertensive effect of amlodipine in essential hypertension patients.METHODS:Genotyping of PXR11193TC and 8055 CT were determined by pyrosequencing sequenator.PXR~*1B was analyzed by PHASE V.2.1.62 essential hypertension 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 PXR11193TC,8055 CT and PXR1B(P0.05).CONCLUSION:PXR polymorphisms does not significantly affect the steady-state trough concentration and antihypertensive effect of amlodipine in essential hypertension patients.
出处 《中国临床药理学与治疗学》 CAS CSCD 2010年第10期1143-1147,共5页 Chinese Journal of Clinical Pharmacology and Therapeutics
基金 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)
关键词 孕烷X受体 基因多态性 氨氯地平 浓度 降压疗效 Pregnane X receptor Gene polymorphism Amlodipine Concentration Antihypertensive
  • 相关文献

参考文献11

  • 1陈卿,吴健,伍建红,罗晓波,李正初.高血压患者长期服用氨氯地平对动脉弹性和左心室肥大的影响[J].中国动脉硬化杂志,2007,15(7):503-505. 被引量:10
  • 2Park JY, Kim KA, Lee GS, ctal. Randomized, open label, two period crossover comparison of the pharmacokinetic and pharmacodynamic properties of two amlodipine formulations in healthy adult male Korean subjects[J].Clin Ther, 2004, 26 ( 5 ) :715-723. 被引量:1
  • 3Kim KA. Park PW. Lee OJ, et al. Effect of CYP3A5 * 3 genotype on the pharmacokinctics and pharmacodynamics of amlodipine in heahhy Korean subjects[J].Clin Pharmacol Ther. 2006. 80(6) : 646 - 656. 被引量:1
  • 4Kuchl P, Zhang J. Lin Y, et al, Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expressiona[J].Nat Genet, 2001, 27(1):383- 391. 被引量:1
  • 5Kim KA, Park PW. Park JY. Effect of ABCBI (MDR1) haplotypcs derived from G2677T/C3435T on the pharmacokinetics of amlodipine in healthy subjects[J].Br J Clin Pharmacol, 2007.63(1): 53-58. 被引量:1
  • 6Fukuen S, Fukuda T. Matsuda H. et al. Identification of thc novel splicing variants for the hPXR in human livers[J].Biochem Biophys Res Commun, 2002, 2008(3):433-438. 被引量:1
  • 7Uno Y, Sakamoto Y. Yoshida K, et al. Characterization of six base pair deletion in the putative HNF1 binding site of human PXR promoter[J].J Hum Genet,2003,48(11): 594- 597. 被引量:1
  • 8刘国仗,胡大一,陶萍,诸骏仁,郭林妮,郭静萱,游凯.心血管药物临床试验评价方法的建议[J].中华心血管病杂志,1998,26(1):5-11. 被引量:1440
  • 9Oleson L. von Mohke LL, Greenblatt DJ, et al. I dentification of polymorphisms in the 3'-untranslated region of the human pregnane X receptor (PXR) gene associated with variability in cytochrome P450 3A (CYP3A) metabolism[J].Xenobiotica, 2010, 40(2): 146-162. 被引量:1
  • 10Miura M, Satoh S, Inoue K, et al. Influence of CYP3AS, ABCB1 and NRII2 polymorphisms on prednisolone pharmacokinetics in renal transplant recipients[J]. Steroids, 2008, 73(11): 1052 -1059. 被引量:1

二级参考文献7

共引文献1448

同被引文献66

  • 1李东宝,华琦,皮林,许骥,刘荣坤.G蛋白β3亚单位基因C825T多态性对氨氯地平降压效果的影响[J].首都医科大学学报,2005,26(6):725-728. 被引量:7
  • 2Chen Z,Stamler JS.Bioactivation of nitroglycerin by the mitochondrial aldehyde dehydrogenase[J].Trends Cardio-vasc Med,2006,16(8):259. 被引量:1
  • 3Yoshida A,Huang IY,Ikawa M.Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals[J].Proc Natl Acad,1984,81(1):258. 被引量:1
  • 4Crabb DW,Edenberg HJ,Bosron WF,et al.Genotypes for aldehyde dehydrogenase deficiency and alcohol sensi-tivity.The inactive ALDH2(2)allele is dominant[J].J Clin Invest,1989,83(1):314. 被引量:1
  • 5Li Y,Zhang D,Jin W,et al.Mitochondrial aldehyde de-hydrogenase-2(ALDH2)Glu504Lys polymorphism con-tributes to the variation in efficacy of sublingual nitroglyc-erin[J].J Clin Invest,2006,116(2):506. 被引量:1
  • 6Rau T,Heide R,Bergmann K,et al.Effect of the CYP2D6genotype on metoprolol metabolism persists during long-term treatment[J].Pharmacogenetics,2002,12(6):465. 被引量:1
  • 7Taguchi M,Nozawa T,Mizumaki K,et al.Nonlinear mixed effects model analysis of the pharmacokinetics of metoprolol in routinely treated Japanese patients[J].Biol Pharm Bull,2004,27(10):1642. 被引量:1
  • 8Nozawa T,Taguchi M,Tahara K,et al.Influence of CYP2D6genotype on metoprolol plasma Concentration andβ-adrenergic inhibition during long-term treatment:a com-parison with bisoprolol[J].Cardiovasc Pharmacol,2005,46(5):713. 被引量:1
  • 9Issam Zineh,Amber L,Beitelshees,et al.Pharmacoki-netics and CYP2D6genotypes do not predict metoprolol adverse events or efficacy in hypertension[J].Clin Phar-macol Ther,2004,76(6):536. 被引量:1
  • 10Rau T,Wuttke H,Michels LM,et al.Impact of the CYP2D6genotype on the clinical effects of metoprolol:a prospective longitudinal study[J].Clin Pharmacol Ther,2009,85(3):269. 被引量:1

引证文献3

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部