MDR1基因C3435T多态性对替米沙坦血药浓度与药动学的影响

目的：探讨健康志愿者和高血压患者的多药耐药基因26（exon26）C3435T基因多态性对替米沙坦的血药浓度和药动学的影响。方法：采用聚合酶链反应（PCR）和限制性内切片段多态性（RFLP）的方法对19例健康志愿者和66例高血压患者进行MDR1基因分型。使用HPLC-MS法测定健康志愿者单剂量口服40mg替米沙坦48h内血药浓度和高血压患者的稳态血药浓度。比较不同基因型之间替米沙坦在健康志愿者的药物动力学的差异，和高血压患者的稳态血药浓度差异。结果：C3435T发生率在健康人群和高血压患者之间没有明显的差异，C3435T的3个不同基因型健康志愿者的Cmax，tmax，AUC0-48，AUC0-∞，CL差异无统计学意义（P〉0．05）。3个基因型的高血压患者的稳态血药浓度差异无统计学意义（P〉0．05）。结论：MDR1C3435T基因多态性对替米沙坦的血药浓度和药动学无影响。

Effects of MDR1 Gene C3435T Polymorphism on Blood Concentration and Pharmacokinetics of Telmisartan

Objective： To determine the effects of MDR1 C3435T on the pharmacokinetics of lelmisartan in healthy Chinese volunteers and blood concentrations in hypertension patients. Method： The genotype on MDR1 C3435T in 19 healthy Chinese volunteers who were received a single oral dose of40mg telmisartan and 66 hypertension patients who were received oral of40mg telmisartan every day after a month was detected by PCR RFLP method , the relationship of MDR1 C3435T polymorphism and steady-state 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 MDR1 C3435T genotypes. Result： There were no difference between normal people and hypertension patients in MDR1 C3435T distribution. No significant difference in Cmax ,tmax, t1/2 , AUC0-48 , AUC0- ∞ and CL among MDR1 C3435T genotypes in healthy volunteers and no significant difference in steady-state concentration among MDR1 C3435T genotypes in hypertension patients was observed. Conclusions： The MDR1 C3435T polymorphism does not affect the blood concentration and pharmaeokineties of telmisartan.