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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C_(max),t_(max),AUC_(0-48),AUC_(0-∞),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。
Objective: To investigate the effects of multi-drug resistant gene 26 (exon26) C3435T gene polymorphism on blood concentration and pharmacokinetics of telmisartan in healthy volunteers and hypertensive patients. Methods: MDR1 genotyping was performed in 19 healthy volunteers and 66 hypertensive patients by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The plasma concentration of telmisartan and the steady-state plasma concentration of hypertensive patients were determined by HPLC-MS method. The difference in pharmacokinetics of telmisartan among healthy volunteers was compared between different genotypes and in patients with hypertension. RESULTS: The incidence of C3435T was not significantly different between healthy subjects and hypertensive patients. The C max, t max, AUC 0-48 and AUC 0 of the three C3435T genotypes -∞), CL difference was not statistically significant (P> 0.05). There was no significant difference in steady-state plasma concentration of 3 genotypes of hypertensive patients (P> 0.05). Conclusion: MDR1C3435T gene polymorphism has no effect on plasma concentration and pharmacokinetics of telmisartan.