MDR1基因C3435T多态性对替米沙坦稳态血药浓度及降压疗效的影响

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (6): 670-676.

MDR1基因C3435T多态性对替米沙坦稳态血药浓度及降压疗效的影响

范秀珍¹, 郭歆², 王华杰¹, 程泽能²

¹湖南省邵阳市第一人民医院药剂科, 邵阳 422000, 湖南;
²中南大学药学院, 长沙 410013, 湖南

收稿日期:2009-02-02 修回日期:2009-07-12 出版日期:2009-06-26 发布日期:2020-10-27
通讯作者: 程泽能, 男, 教授, 硕导, 研究方向:临床药理学与药代动力学研究。Tel:0731-2650446 E-mail:chengzenengcsu@yahoo.com.cn
作者简介:范秀珍,女,硕士,副主任药师,研究方向:临床药理学。Tel:0739-5228079 E-mail:fanxiuz@sina.com

Effects of MDR1 gene C3435T polymorphism on the steady-state plasma concentration and hypotensive activity of telmisartan

FAN Xiu-zhen¹, GUO Xin², WANG Hua-jie¹, CHENG Ze-neng²

¹Department of Pharmacy, First People's Hospital of Shaoyang, Shaoyang 4220002, Hunan, China;
²School of Pharmaceutical Science, Central South University, Changsha 410013, Hunan, China

Received:2009-02-02 Revised:2009-07-12 Online:2009-06-26 Published:2020-10-27

摘要/Abstract

摘要： 目的: 探讨多药耐药基因MDR1 C3435T(exon 26) 位点基因多态性对替米沙坦在原发性高血压患者中的稳态血药浓度及降压疗效的影响。方法: 采用聚合酶链反应(PCR) 和限制性内切酶片段多态性(RFLP) 的方法对连续30 d 每天口服40 mg 替米沙坦的61 名高血压患者的MDR1 C3435T 位点进行基因分型。使用高效液相色谱-荧光检测法(HPLC-FLD) 测定高血压患者的稳态血药浓度, 使用水银血压计测量治疗前、后高血压患者的血压值。比较不同基因型间高血压患者的稳态血药浓度及降压疗效的差异。结果: 在61 例中老年原发性高血压患者中, MDR1 C3435T CC 型纯合子的频率为39.34%, TT 型纯合子的频率为11.48%, CT 型杂合子的频率为49.18%, MDR1 C3435T 位点等位基因发生率在健康人群和高血压患者间差异无统计学意义。3 种基因型高血压患者的稳态血药浓度及降压有效率间差异无统计学意义(P>0.05) 。结论: MDR1 C3435T 位点的基因多态性与高血压患者的稳态血药浓度及降压疗效间无相关性。

关键词: 多药耐药基因, P-糖蛋白, 单核苷酸多态性, 替米沙坦, 稳态血药浓度

Abstract: AIM: To study the effects of MDR1 C3435T polymorphism on steady-state plasma concentration and hypotensive activity of telmisartan. METHODS: 61 cases of essential hypertension patients were received oral dose of 40 mg telmisartan per day for 30 days.The genotyping of the MDR1 C3435T polymorphism in the patients was performed by using method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).The plasma concentrations of telmisartan were determined by high performance liquid chromatograpy-Fluorescence detector (HPLC-FLD).The blood pressures of the patients were measured before and after treatment.The plasma concentrations and therapeutic effect of telmisartan were compared among the three different genotype groups. RESULTS: Among the 61 cases of elderly hypertension patients, the frequencies of 3435CC, 3435TT and 3435CT were 39.34%, 11.48% and 49.18%, respectively.There were no differences between healthy people and the hypertension patients in allele frequencies of MDR1 C3435T.The telmisartan steady-state concentration and curative effect also had no significant differences among the three genotype groups in the hypertensive patients. CONCLUSION: The MDR1 C3435T polymorphism does not affect the steady-state plasma concentrate and curative effect of telmisartan in hypertension patients.

Key words: multidrug resistance gene, P-glycoprotein, single nucleotide polymorphisms, telmisartan, steady-state plasma concentration

中图分类号:

R969

范秀珍, 郭歆, 王华杰, 程泽能. MDR1基因C3435T多态性对替米沙坦稳态血药浓度及降压疗效的影响[J]. 中国临床药理学与治疗学, 2009, 14(6): 670-676.

FAN Xiu-zhen, GUO Xin, WANG Hua-jie, CHENG Ze-neng. Effects of MDR1 gene C3435T polymorphism on the steady-state plasma concentration and hypotensive activity of telmisartan[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(6): 670-676.

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