Impact of CYP2D6 genotype on adverse effects during treatment with metoprolol:: A prospective clinical study
Impact of CYP2D6 genotype on adverse effects during treatment with metoprolol:: A prospective clinical study
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DOI：
10.1016/j.clpt.2005.07.004
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发表时间：
2005-10-01
影响因子：
6.7
通讯作者：
Kivistö, KT
中科院分区：
文献类型：
--
作者：
Fux, R;Mörike, K;Kivistö, KT
目的：研究细胞色素P450（CYP 2136）基因多态性对美托洛尔耐受性的影响。在现实生活中的初级保健设置。研究的不良反应包括与中枢神经系统、心血管效应和性功能障碍相关的影响。考虑接受美托洛尔治疗的患者入组这项前瞻性、6周多中心研究。美托洛尔的剂量根据个人情况确定，并可根据临床情况自由调整。约90%病例的治疗适应症为高血压。测量收缩压和舒张压、静息心率、血浆美托洛尔和α-羟基美托洛尔浓度。C γ P2 D 6基因分型覆盖等位基因 *3至 *10和 *41以及重复。通过标准化的评定量表和量表对美托洛尔可能的不良反应进行了为期6周的系统评估。最终研究人群包括121例可评价患者（均为白色患者）;其中，5例超快代谢者（UM）（4.1%）、91例快代谢者（EM）（75%）、21例中代谢者（IM）（17%）和4例慢代谢者（PM）（3.3%）。每日剂量标准化的血浆美托洛尔浓度和稳态时的美托洛尔/α-羟基美托洛尔比值明显受C γ P2 D 6基因型的影响，并显示出基因-剂量效应。UMS、EM、IM和PM的剂量标准化美托洛尔浓度中位数分别为0.0088 ng/mL、0.047 ng/mL、0.34 ng/mL和1.34 ng/mL（P
Objective: Our objective was to study the impact of the cytochrome P450 (CYP) 2136 polymorphism on the tolerability of metoprolol. in a real-life primary care setting. The adverse effects studied comprised effects related to the central nervous system, cardiovascular effects, and sexual dysfunction.Methods. Patients in whom treatment with metoprolol was considered were enrolled into this prospective, 6-week multicenter study. The dosage of metoprolol was determined on an individual basis and could be freely adjusted on clinical grounds. The indication for treatment was hypertension in about 90% of cases. Systolic and diastolic blood pressure, resting heart rate, and plasma metoprolol and alpha-hydroxymetoprolol concentrations were measured. C gamma P2D6 genotyping covered alleles *3 to *10 and *41 and the duplications. Possible adverse effects of metoprolol were systematically assessed over a 6-week period by-means of standardized rating scales and questionnaires.Results. The final study population comprised 121 evaluable patients (all white patients); among them, there were 5 ultrarapid metabolizers (UMs) (4.1%), 91 extensive metabolizers (EMs) (75%), 21 intermediate metabolizers (IMs) (17%), and 4 poor metabolizers (PMs) (3.3%). Plasma metoprolol concentrations normalized for the daily dose and metoprolol/alpha-hydroxymetoprolol ratios at steady state were markedly influenced by C gamma P2D6 genotype and displayed a gene-dose effect. The median of the dose-normalized metoprolol concentration was 0.0088 ng/mL, 0.047 ng/mL, 0.34 ng/mL, and 1.34 ng/mL among UMs, EMs, IMs, and PMs, respectively (P