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目的:观察CYP2D6＊10基因型对普罗帕酮在室性心律失常病人中药效学的影响.方法:选择17名室性早搏(VPC≥1000/d)病人.受试者常规实验室检查结果正常,每日3次、每次口服普罗帕酮片剂150-200 mg.于给药前与给药后7 d测定病人心电图和24 h动态心电图(Holter).普罗帕酮稳态峰、谷浓度采用高效液相色谱分析法测定.采用聚合酶链反应(PCR)和限制性片断长度多态性(RFLP)测定CYP2D6＊10基因型.结果:17例室性心律失常病人应用普罗帕酮后,室性早搏总抑制率为79.9％,PR间期延长从0.146 s±0.018 s增加到0.161 s±0.022 s(P<0.05).CYP2D6基因型在普罗帕酮血浆浓度和效应中起着重要作用.450 mg/d剂量组中具有CYP2D6*10 突变纯合子的病人,普罗帕酮血浆峰浓度约为野生基因型的二倍,而且VPC抑制率也增加一倍(P<0.05).结论:CYP2D6＊10基因型与中国心律失常病人CYP2D6酶活性下降有关.普罗帕酮血浆峰浓度增加与室性早搏病人疗效改善相一致.
Objective: To investigate the effect of CYP2D6 * 10 genotype on the pharmacodynamics of propafenone in patients with ventricular arrhythmias.Methods: Seventeen patients with premature ventricular contractions (VPC≥1000 / d) were selected.The routine laboratory test results Normal, three times a day, each oral propafenone tablet 150-200 mg before treatment and 7 d after administration of the patient’s electrocardiogram and 24 h Holter, propafenone steady-state peak, Valley The concentration of CYP2D6 * 10 was determined by high performance liquid chromatography (HPLC), and the genotypes of CYP2D6 * 10 were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) .Results: Seventeen patients with ventricular arrhythmia , The total inhibitory rate of premature ventricular contraction was 79.9%, and the prolongation of PR interval increased from 0.146 s ± 0.018 s to 0.161 s ± 0.022 s (P <0.05) .CYP2D6 genotype played an important role in propafenone plasma concentration and effect In patients with a homozygote of CYP2D6 * 10 mutation in the 450 mg / d dose group, the peak plasma concentration of propafenone was about twice as high as that of the wild-type genotype, and the VPC inhibition rate was also doubled (P <0.05) .Conclusion: CYP2D6 * 10 genotype and Chinese patients with arrhythmia decreased CYP2D6 activity related to propafenone plasma peak concentration increased Consistent with the patient to improve the efficacy of premature ventricular contractions.