MDR1基因多态性对替米沙坦血药浓度和药动力学影响研究

Effects of MDRl Gene C3435T polymorphism on bloold concentration and pharmacokinetics of telmisartan

目的:探讨健康志愿者和高血压患者的多药耐药基因(Multidrug resistance 1 gene,MDR1)C3435T基因多态性对替米沙坦血药浓度和药动学的影响。方法:采用聚合酶链反应(Polymerase chain reaction,PCR)和限制性内切片段多态性(Restriction fragment length poly-morphism,RFLP)的方法对19名健康志愿者和61例高血压患者进行MDRl基因分型;使用HPLC-MS法测定志愿者单剂量口服40mg替米沙坦48h内血药浓度和高血压患者的稳态血药浓度。比较替米沙坦在不同基因型的健康志愿者单剂量药动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,MDRlCC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之间没有明显的差异,C3435T的三个不同基因型志愿者Cmax、tmax、t1/2、AUC0-48、AUC0-∞和CL差异无统计学意义(P>0.05)。三个基因型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:MDRlC3435T基因多态性对替米沙坦的血药浓度和药动学无影响。

ABSTRACT AIM. To determine the effects of MDRIC3435T on the pharmacokinetics of telm- isartan in healthy Chinese volunteers and blood concentration in hypertension patients. METH-ODS： The genotype on MDRIC3435T in 19 healthy Chinese volunteers who were received a single oral dose of 40 ng telmisartan and 61 hy-pertension patients who were received oral of 40 mg telmisartan every day after a month was de-tected by PCR RFLP method, the relationship of MDR1C3435T polymorphism and steady-state blood concentrations of telmisartan were deter-minated by HPLC-MS. The pharmacokinetics of telmisartan in health volunteers and steady-state telmisartan concentrations of patients with hy-pertension were compared among MDRIC3435T 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 were no differences between normal peo-ple and hypertension patients in MDR1 ditribu-tion. No significant difference in Cmax, tmax, t1/2, AUC0-48, AUC0-∞ and CL among MDR1 C3435T genotypes in health volunteers and no significant difference in steady-state concentra-tion among MDR1C3435T genotypes in hyper-tension patients were observed. CONCLUSION： The MDR1 C3435T polymorphism does not af-fect the blood concentration and pharmacokinet-ics of telmisartan.