Effect of CYP2D6~*10 genotype on propafenone pharmacodynamics in Chinese patients with ventricular arrhythmia  

CYP2D6*10基因型对中国室性心律失常病人普罗帕酮药效学的影响(英文)

作　　者：蔡卫民 徐军[1] 陈冰 张馥敏[3] 黄元铸[3] 张银娣 

机构地区：[1]南京金陵医院心脏病科,南京210002 [2]南京金陵医院临床药理科 [3]南京医科大学第一附属医院心脏病科 [4]南京医科大学第一附属医院临床药理研究所,南京中国210029

出　　处：《Acta Pharmacologica Sinica》2002年第11期1040-1044,共5页中国药理学报（英文版）

摘　　要：RAIM: To determine the effect of CYP2D6*10 genotype on propafenone pharmacodynamics in Chinese patients with ventricular arrhythmia. METHODS: Seventeen Chinese patients with ventricular premature contractions (VPC≥1000/d) were recruited. They were normal in routine laboratory testing and administered propafenone hydrochloride 450-600 mg per day in three divided doses. Twelve lead cardiogram and 24 h Holter monitoring were performed before and after 7 d treatment of propafenone. Steady-state peak and trough concentrations of propafenone were measured by HPLC method. CYP2D6*10 genotypes of patients were assayed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: Total inhibitory rate of VPC was 79.9 % in 17 patients with ventricular arrhythmia after propafenone treatment. PR interval prolongation was increased from 0.146 s?.018 s to 0.161 s?.022 s (P<0.05). CYP2D6 genotypes played an important role in plasma levels and effects of propafenone. In 450 mg/d group, patients with homozygous mutant of CYP2D6* 10 not only had a Cmax of propafenone two times as high as those of wild-type genotype, but also showed a two fold higher inhibitory rate of VPC compared with those with homozygous CYP2D6*1 (P<0.05). CONCLUSION: CYP2D6*10 geno-type is relevant to decreased activity of CYP2D6 enzyme in Chinese patients. Elevated plasma concentration is consistent with better efficacy of propafenone in patients with ventricular arrhythmia.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.

关 键 词：PROPAFENONE PHARMACODYNAMICS cytochrome P-450 CYP2D6 ventricular dysfunction GENOTYPE 

分 类 号：R96[医药卫生—药理学]