Li Shuchun, Lin Han, Sun WenHuan, Wang YingLi, Ding YouFang, Zhao HuanHu, Liu ShangJian
Int J Clin Pharmacol Ther. 2017 Jun;55(6):483-492. doi: 10.5414/CP202545.
To conduct a meta-analysis on the effect of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamics of metoprolol.
A systematic review and meta-analysis of studies on the effect of CYP2D6 polymorphism on metoprolol pharmacokinetics and pharmacodynamics was performed by using the China national knowledge infrastructure (CNKI), database for Chinese technical periodicals (VIP), Wanfang, and PubMed databases up to the end of January 2015. Review Manager 5.3 (the coherence collaboration, www.gradepro.org) and comprehensive Meta-Analysis Software v2 (CMA) Biostat, Englewood, NJ, USA) were used for meta-analysis.
A total of 567 cases from 7 studies were included in the present study. Meta-analysis results showed that the area under the curve (AUC) (RR = -6.75, 95% CI (-9.18, -4.31), p < 0.00001); C (RR = -2.40, 95% CI (-3.25, -1.54), p < 0.00001); T (RR = -4.81, 95% CI (-6.86, -2.76), p < 0.00001); CL/F (RR = 1.60, 95% CI (1.03,2.17), p < 0.00001); heart rate (RR = 1.48, 95% CI (0.03, 2.92), p = 0.05), systolic blood pressure (RR = -0.69, 95% CI (-1.85,0.47), p = 0.24); and diastolic blood pressure (RR = -1.95, 95% CI (-3.14, -0.76), p = 0.001). Begg's funnel plot test showed that the pharmacokinetic parameters (AUC, C, T, and CL/F) and pharmacodynamic parameters (HR, DBP, and SBP) were symmetric. Egger's test showed that the pharmacokinetic parameters were asymmetrical, and its intercept was statistically significant (p < 0.05), which was indicative of publication bias. The pharmacodynamic parameter intercept was not statistically significant (p > 0.05), indicating that no publication bias existed.
CONCLUSION: CYP2D6 polymorphism significantly influenced the pharmacokinetic parameters of metoprolol. It also affected heart rate and diastolic blood pressure, whereas systolic pressure was not affected. .
对CYP2D6基因多态性对美托洛尔药代动力学和药效学的影响进行荟萃分析。
利用中国知网（CNKI）、中文科技期刊数据库（维普）、万方数据库以及截至2015年1月底的PubMed数据库，对关于CYP2D6基因多态性对美托洛尔药代动力学和药效学影响的研究进行系统评价和荟萃分析。采用Review Manager 5.3（一致性协作组，www.gradepro.org）和综合Meta分析软件v2（CMA，美国新泽西州恩格尔伍德市Biostat公司）进行荟萃分析。
本研究共纳入7项研究中的567例病例。荟萃分析结果显示，曲线下面积（AUC）（RR = -6.75，95%CI（-9.18，-4.31），p < 0.00001）；血药浓度（C）（RR = -2.40，95%CI（-3.25，-1.54），p < 0.00001）；达峰时间（T）（RR = -4.81，95%CI（-6.86，-2.76），p < 0.00001）；清除率/分布容积（CL/F）（RR = 1.60，95%CI（1.03，2.17），p < 0.00001）；心率（RR = 1.48，95%CI（0.03，2.92），p = 0.05），收缩压（RR = -0.69，95%CI（-1.85，0.47），p = 0.24）；舒张压（RR = -1.95，95%CI（-3.14，-0.76），p = 0.001）。Begg漏斗图检验显示，药代动力学参数（AUC,C,T和CL/F）和药效学参数（HR,DBP和SBP）呈对称分布。Egger检验显示，药代动力学参数呈不对称分布，其截距具有统计学意义（p < 0.05），提示存在发表偏倚。药效学参数截距无统计学意义（p > 0.05），表明不存在发表偏倚。
CYP2D6基因多态性显著影响美托洛尔的药代动力学参数，同时也影响心率和舒张压，但对收缩压无影响。
