title: A meta-analysis of the effect of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamics of metoprolol .
abstract: OBJECTIVE
  To conduct a meta-analysis on the effect of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamics of metoprolol.
  
  
  METHODS
  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.
  
  
  RESULTS
  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)0-∞(RR = -6.75, 95% CI (-9.18, -4.31), p < 0.00001); Cmax(RR = -2.40, 95% CI (-3.25, -1.54), p < 0.00001); T1/2(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 (AUC0-∞, Cmax, T1/2, 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.
  
  
  CONCLUSIONS
  CYP2D6 polymorphism significantly influenced the pharmacokinetic parameters of metoprolol. It also affected heart rate and diastolic blood pressure, whereas systolic pressure was not affected. .
authors.forename: Shuchun
authors.initials: S
authors.lastname: Li
authors.forename: Han
authors.initials: H
authors.lastname: Lin
authors.forename: WenHuan
authors.initials: W
authors.lastname: Sun
authors.forename: YingLi
authors.initials: Y
authors.lastname: Wang
authors.forename: YouFang
authors.initials: Y
authors.lastname: Ding
authors.forename: HuanHu
authors.initials: H
authors.lastname: Zhao
authors.forename: ShangJian
authors.initials: S
authors.lastname: Liu
mesh_terms: D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008790:Metoprolol / Q000493:pharmacokinetics* / Q000494:pharmacology; D011110:Polymorphism, Genetic; D017594:Publication Bias
chemical_list: D019389:Cytochrome P-450 CYP2D6; D008790:Metoprolol