title: Impact of CYP2D6 polymorphisms on clinical efficacy and tolerability of metoprolol tartrate.
abstract: Metoprolol is a selective β-1 adrenergic receptor blocker that undergoes extensive metabolism by the polymorphic enzyme cytochrome P450 2D6 (CYP2D6). Our objective was to investigate the influence of CYP2D6 polymorphisms on the efficacy and tolerability of metoprolol tartrate. Two hundred and eighty-one participants with uncomplicated hypertension received 50 mg of metoprolol twice daily followed by response-guided titration to 100 mg twice daily. Phenotypes were assigned based on results of CYP2D6 genotyping and copy number variation assays. Clinical response to metoprolol and adverse effect rates were analyzed in relation to CYP2D6 phenotypes using appropriate statistical tests. Heart rate response differed significantly by CYP2D6 phenotype (P < 0.0001), with poor and intermediate metabolizers showing greater reduction. However, blood pressure response and adverse effect rates were not significantly different by CYP2D6 phenotype. Other than a significant difference in heart rate response, CYP2D6 polymorphisms were not determinants of variability in metoprolol response or tolerability.
authors.affiliation: Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA.
authors.forename: I S
authors.initials: IS
authors.lastname: Hamadeh
authors.affiliation: Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA.
authors.forename: T Y
authors.initials: TY
authors.lastname: Langaee
authors.affiliation: Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA.
authors.forename: R
authors.initials: R
authors.lastname: Dwivedi
authors.affiliation: Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA.
authors.forename: S
authors.initials: S
authors.lastname: Garcia
authors.affiliation: Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Burkley
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Skaar
authors.affiliation: Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Chapman
authors.affiliation: 1] Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, Florida, USA [2] Department of Community Health and Family Medicine, University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Gums
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Turner
authors.affiliation: Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Gong
authors.affiliation: 1] Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA [2] Division of Cardiology, Department of Medicine, University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Cooper-DeHoff
authors.affiliation: 1] Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA [2] Division of Cardiology, Department of Medicine, University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003863:Depression / Q000139:chemically induced / Q000175:diagnosis; D005221:Fatigue / Q000139:chemically induced / Q000175:diagnosis; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008790:Metoprolol / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D019389:Cytochrome P-450 CYP2D6; D008790:Metoprolol