학술논문
Impact of CYP2D6 polymorphisms on clinical efficacy and tolerability of metoprolol tartrate.
Document Type
Academic Journal
Author
Hamadeh IS; Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA.; Langaee TY; Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA.; Dwivedi R; Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA.; Garcia S; Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA.; Burkley BM; Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA.; Skaar TC; Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Chapman AB; Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.; Gums JG; 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.; Turner ST; Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.; Gong Y; Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA.; Cooper-DeHoff RM; 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.; Johnson JA; 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.
Source
Publisher: Wiley Country of Publication: United States NLM ID: 0372741 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-6535 (Electronic) Linking ISSN: 00099236 NLM ISO Abbreviation: Clin Pharmacol Ther Subsets: MEDLINE
Subject
Language
English
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.