MDR1 C3435T基因多态性对替米沙坦药代动力学的影响  

Effects of MDR1 gene C3435T polymorphism on pharmacokinetics of telmisartan

作　　者：林惊世 徐察 李毓芹 王齐增 

机构地区：[1]温岭市第一人民医院药剂科,浙江温岭317500

出　　处：《中国临床药理学杂志》2013年第8期609-612,共4页The Chinese Journal of Clinical Pharmacology

基　　金：温岭市科技局基金资助项目(2011WLCB0102)

摘　　要：目的探讨健康志愿者和高血压患者的多药耐药基因(MDR1)C3435T基因多态性对替米沙坦药代动力学的影响。方法用聚合酶链反应(PCR)和限制性内切片段多态性(RFLP)方法对19名健康志愿者和61例高血压患者进行MDRl基因分型;用HPLC-MS法测定健康志愿者单剂量口服替米沙坦40 mg后48 h内血药浓度和高血压患者的稳态血药浓度。比较替米沙坦在不同基因型的健康志愿者单剂量药代动力学及高血压患者稳态血药浓度的差异。结果在61例高血压患者中,MDRl CC型纯合子频率39.34%,TT型纯合子频率11.48%。CT型杂合子频率49.18%,C3435T发生率在健康人群和高血压患者间差异无统计学意义。C3435T的3个不同基因型志愿者Cmax,tmax,t1/2,AUC0-48 h,AUC0-∞和CL差异无统计学意义(P>0.05)。3个基因型高血压患者稳态血药浓度差异无统计学意义(P>0.05)。结论 MDRl C3435T基因多态性对替米沙坦的药代动力学无影响。Objective To determine the effects of MDR1C3435T on the pharmacokinetics of telmisartan.Methods The genotype on MDR1C3435T in 19 healthy Chinese volunteers who received a single oral dose of 40 mg telmisartan and 61 hypertension patients who orally received 40 mg telmisartan every day after a month was detected by PCR RFLP method.The blood concentrations of telmisartan were determinated by HPLC-MS.The pharmacokinetics of telmisartan in health volunteers and steady-state telmisartan concentrations of patients with hypertension were compared among MDR1C3435T genotypes.Results Among the 61 cases of hypertension patients,the frequencies of C3435T CC,C3435T TT and C3435T CT were 39.34%,11.48% and 49.18%,respectively.There was no difference between normal people and hypertension patients on MDR1 distribution.No significant difference of Cmax,tmax,t1/2,AUC0-48 h,AUC0-∞ and CL among MDR1 C3435T genotypes in health volunteers and steady-state concentrations among MDR1C3435T genotypes in hypertension patients was observed.Conclusion The MDR1 C3435T polymorphism does not affect the pharmacokinetics of telmisartan.

关 键 词：替米沙坦 药物动力学 稳态浓度 多药耐药基因 

分 类 号：R972.4[医药卫生—药品]