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- Title
Impact of CYP2D6 Polymorphisms on Clinical Efficacy and Tolerability of Metoprolol Tartrate.
- Authors
Hamadeh, I S; Langaee, T Y; Dwivedi, R; Garcia, S; Burkley, B M; Skaar, T C; Chapman, A B; Gums, J G; Turner, S T; Gong, Y; Cooper‐DeHoff, R M; Johnson, J A
- 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.
- Subjects
METOPROLOL; DRUG tolerance; DRUG efficacy; ADRENERGIC beta blockers; CYTOCHROME P-450 CYP2D6; DRUG side effects; HEART beat
- Publication
Clinical Pharmacology & Therapeutics, 2014, Vol 96, Issue 2, p175
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1038/clpt.2014.62