Effect of CYP2D6 genetic polymorphism on peak propafenone concentration: no significant effect of CYP2D6*10
Effect of CYP2D6 genetic polymorphism on peak propafenone concentration: no significant effect of CYP2D6*10
复制标题
CYP2D6基因多态性对普罗帕酮峰值浓度的影响：该基因对普罗帕酮浓度无显著影响
DOI：
10.2217/pgs-2020-0105
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发表时间：
2020-11-18
期刊：
影响因子：
2.1
通讯作者：
Homma, Masato
中科院分区：
文献类型：
--
作者：
Doki, Kosuke;Shirayama, Yuki;Homma, Masato
目的：本研究旨在探讨CYP 2D 6的非功能性弱代谢型（PM）等位基因和中间代谢型（IM）等位基因（包括CYP 2D 6 *10等位基因，该等位基因显示底物依赖性酶活性降低）在普罗帕酮抗心律失常治疗中的临床意义。材料和方法：我们检查了66例日本快速性心律失常患者的血清普罗帕酮浓度和代谢比，代谢比表示为普罗帕酮与5-羟基普罗帕酮的血清浓度。结果如下：CYP 2D 6 PM等位基因携带者的普罗帕酮峰浓度和代谢率高于EM/EM、EM/IM和IM/IM基因型组。结论：结果表明，CYP 2D 6 PM等位基因影响普罗帕酮峰浓度，但CYP 2D 6 IM等位基因CYP 2D 6 *10对普罗帕酮给药无临床意义。
Aim: The study aims to investigate the clinical implication of nonfunctional poor metabolizer (PM) alleles and intermediate metabolizer (IM) alleles of CYP2D6, including the CYP2D6*10 allele which shows substrate-dependent decrease in enzymatic activity, in antiarrhythmic therapy using propafenone. Materials & methods: We examined serum propafenone concentrations and metabolic ratio, which was expressed as serum concentrations of propafenone to 5-hydroxypropafenone, in 66 Japanese patients with tachyarrhythmias. Results: The peak propafenone concentration and metabolic ratio in CYP2D6 PM allele carriers were higher than those in extensive metabolizer (EM)/EM, EM/IM and IM/IM genotype groups. Conclusion: Results suggest that CYP2D6 PM alleles affect peak propafenone concentration, but the CYP2D6 IM allele CYP2D6*10 has no clinical implication in propafenone dosing.