基因多态性对氨氯地平药代、药效的影响

摘要/Abstract

摘要： 氨氯地平是二氢吡啶钙离子通道阻滞剂,临床上用于各种高血压和心绞痛的治疗,在体内经CYP3A5代谢而消除,其药代动力学不同于其他的二氢吡啶钙离子通道阻滞剂。由于CYP3A存在基因多态性而导致氨氯地平药代动力学的个体差异。为此,笔者查阅国内外相关文献对氨氯地平的临床应用与CYP3A5基因多态性对其药代动力学及药效学的影响进行综述,为临床参考基因多态性特征来确立氨氯地平正确合理的给药方案提供依据。

关键词: CYP3A5, 氨氯地平, 药动学, 药效学

Abstract: Amlodipine, 1,4-Dihydropyridine calcium channel antagonists, prescribed in the management of angina and hypertension, act as substrates of CYP3A5, has a pharmacokinetic profile that differs from other dihydropyridines.It has been suggested that the CYP3A5^*3 allele contributes to the interindividual variability of CYP3A activity in vivo. This review aimed to summarize the clinical application of the amlodipine and the possible role of the genetic polymorphism CYP3A5 on the pharmacokinetics and pharmacodynamics of amlodipine and instruct the reasonable clinical application of amlodipine.

Key words: CYP3A5, Amlodipine, Pharmacokinetics, Pharmacodynamics

中图分类号:

R969

杨夏玲, 杨婧芝, 熊玉卿. 基因多态性对氨氯地平药代、药效的影响[J]. 中国临床药理学与治疗学, 2011, 16(4): 455-460.

YANG Xia-ling,YANG Jing-zhi, XIONG Yu-qing. Effects of polymorphic gene on the pharmacokinetics and pharmacodynamics of amlodipine[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(4): 455-460.

参考文献

[1] 马建林,毛焕元. 长效钙离子颉颃剂氨氯地平的作用特点及其临床应用[J].中国医院药学杂志,1995,15(11):524-525.
[2] 夏青. 氨氯地平的药理和临床应用 [J]. 中外医疗,2008,25:86-87.
[3] 史晏海,凌华伟. 新型钙离子颉颃剂氨氯地平 [J]. 中国新药杂志,1995,4(5):9-l1.
[4] Cappuccio FP , Markandu ND, Sagnella GA, et al. Effects on urinary sodium excretion, renin- angiotensin-aldosterone system,atrial natriuretic peptide and blood pressure in essential hypertension[J]. Human Hypertension,1991,5(2):115-119.
[5] Julius S. Amlodipine in hypertension an overview of the clinical dossier [J]. Cardiovasc Pharmcol,1988,12 (7):S27-33.
[6] 赵素芳. 苯磺酸左旋氨氯地平治疗轻中度高血压疗效观察[J]. 山西医药杂志,2009,38(1):23-24.
[7] 高智平. 新型钙颉颃剂一氨氯地平[J]. 广东药学,1999,9(3):53-54.
[8] 郑银香. 苯磺酸左旋氨氯地平治疗冠心病心绞痛临床观察[J]. 浙江临床医学, 2003,5 (10):779-780.
[9] Va1carce1 Y, Jimenez R, Hernandez V, et al. Efficacy and safety of amlodipine[J]. Authors and Disciosures Published,4,6,2006
[10] Kuehl P, Zhang J, Lin Y, el a1. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression[J]. Nat Genet,2001,27(4):383.
[11] Saeki M, Saito Y, Nakamura T, et al. Single nucleotide polymorphisms(SNPs) haplotype frequencies of CYP3A5 in a Japanese population[J]. Hum Mut,2003,21(6):653-660.
[12] Zheng H, Zeevi A, Schuetz E,et al. Tacrolimus dosing in adult lung transplant patients is relate to cytochrome P4503A5 gene polymorphism[J].Clin Pharnacol,2004,44(2):135-140.
[13] Hu YF, He J, Chen GL, et al. CYP3A5^*3 andCYP3A4^*18 single nucleotide polymorphisms in a Chinese popu-lation[J]. Clin Chim Acta,2005,353(1/2):187.
[14] Ozdemir V, Kalow W,Tang BK, et al. Evaluation of the genetic component of variability in CYP3A4 activity: a repeated drug administration method[J]. Pharmacogenetics,2000,10(5):373-388.
[15] Evans WE, Mcleod HL. Pharmacogenomics-drug disposition,drug targets and side effects [J]. N Engl Med, 2003,348(6):538-549.
[16] Evans WE, Relling MV. Pharmacogenetics:translating functional genomics into rational therapeutics[J]. Science,1999,286:487-491.
[17] Beresford AP, Macrae PV, Alker D, et al. Biotransformation of amlodipine. Identification and synthesis of metabolites found in rat, dog and human urine/confirmation of structures by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry[J]. Arzneimittel forschung,1989,39(2):201-209.
[18] Walker DK, Humphrey MJ, Smith DA. Importance of metabolic stability and hepatic distribution to the pharmacokinetic profile of amlodipine[J]. Xenobiotica,1994,24(3):243-250.
[19] Josefsson M, Zackrisson AL, Ahlner J. Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers[J]. Eur J Clin Pharmacol,1996,51(2):189-193.
[20] Glesby MJ, Aberg JA, Kendall MA, et al. Pharmacokinetic interactions between indinavir plus ritonavir and calcium channel blockers[J]. Clin Pharmacol Ther,2005,78(2):143-153.
[21] Emoto C, Iwasaki K. Enzymatic characteristics of CYP3A5 and CYP3A4: a comparison of in vitro kinetic and drug-drug interaction patterns[J]. Xenobiotica,2006,36(2/3):219-233.
[22] Mouly SJ, Matheny C, Paine MF, et al. Variation in oral clearance of saquinavir is predicted by CYP3A5^*1 genotype but not by enterocyte content of cytochrome P450 3A5[J]. Clin Pharmacol Ther, 2005,78(6):605-618.
[23] Wong M, Balleine RL, Collins M, et al. CYP3A5 genotype and midazolam clearancein Australian patients receiving chemotherapy[J]. Clin Pharmacol Ther,2004,75(6):529-538.
[24] Park JY, Kim KA, Park PW, et al. Effect of CYP3A5^*3 genotype on the pharmacokinetics and pharmacodynamics of alprazolam in healthy subjects[J]. Clin Pharmacol Ther ,2006,79(6):590-599.
[25] Suh JW, Koo BK, Zhang SY, et al. Increased risk of atherothrombotic events associated with cytochrome P450 3A5 polymorphism in patients taking clopidogrel[J]. CMAJ ,2006,174(12):1715-1722.
[26] Balram C, Zhou Q, Cheung YB, et al. CYP3A5^*3 and ^*6 single nucleotide polymorphisms in three distinct Asian populations[J]. Eur J Clin Pharmacol,2003,59(2):123-126.
[27] Fukushima-Uesaka H, Saito Y, Watanabe H, et al. Haplotypes of CYP3A4 and their close linkage with CYP3A5 haplotypes in a Japanese population[J]. Hum Mutat ,2004,23(1):100.
[28] Plummer SJ, Conti DV, Paris PL, et al. CYP3A4 and CYP3A5 genotypes, haplotypes,and risk of prostate cancer[J]. Cancer Epidemiol Biomarkers Prev,2003,12(9):928-932.
[29] Lamba JK, Lin YS, Schuetz EG, et al. Genetic contribution to variable human CYP3A-mediated metabolism[J]. Adv Drug Deliv Rev,2002,54(10):1271-1294.
[30] Xie HG, Wood AJ, Kim RB, et al. Genetic variability in CYP3A5 and its possible consequences[J]. Pharmacogenomics, 2004,5(3):243-272.
[31] Dai D, Tang J, Rose R, et al. Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos[J]. Pharmacol Exp Ther,2001,299(3):825-831.
[32] Eiselt R, Domanski TL, Zibat A, et al. Identification and functional characterization of eight CYP3A4 protein variants[J]. Pharmacogenetics, 2001,11(5):447-458.
[33] Hoffmeyer S, Burk O, von Richter O, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo[J]. Proc Natl Acad Sci USA,2000,97(7):3473-3478.
[34] Vincent J, Harris SI, Foulds G,et al. Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine[J].Br J Clin Pharmacol ,2000,50(5):455-463.
[35] Josefsson M, Ahlner J. Amlodipine and grapefruit juice[J]. Br J Clin Pharmacol ,2002,53(4):405.
[36] Bailey DG, Malcolm J, Arnold O, et al. Grapefruit juice-drug interactions[J]. Br J Clin Pharmacol,1998,46(2):101-110.
[37] Hochman JH, Chiba M, Nishime J, et al. Influence of P-glycoprotein on the transport and metabolism of indinavir in Caco-2 cells expressing cytochrome P450 3A4[J]. Pharmacol Exp Ther, 2000,292(1):310-318.
[38] Gorski JC, Vannaprasaht S, Hamman MA, et al. The effect of age, sex, and rifampin administration on intestinal and hepatic cytochrome P450 3A activity[J]. Clin Pharmacol Ther,2003,74(3):275-287.
[39] 储小曼,郭联庆,黄苍龙. CYP3A5和MDR1基因多态性对阿奇霉素药代动力学的影响[J]. 中国药科大学学报,2007,38(2):167-171.
[40] Chowbay B,Cumaraswmy S, Cheung YB, et al. Genetic polymorphisms in MDR1 and CYP3A4 genes in Asians and the influence of MDR1 hap lotypes on cycolsporin dispositon in heart transp lant recip ients[J]. Pharmcogenetics,2003,13:89-95.
[41] David IM, Vicki LE, Sharon M,et al. CYP3A3 polymorphism and the ethnic differences in cyclosporine pharmacokinetics in healthy subjects[J].Ther Drug Monit, 2004,26(5):534-528.