Impact of CYP2D6 polymorphisms on clinical efficacy and tolerability of metoprolol tartrate

I. S. Hamadeh, T. Y. Langaee, R. Dwivedi, S. Garcia, B. M. Burkley, Todd Skaar, A. B. Chapman, J. G. Gums, S. T. Turner, Y. Gong, R. M. Cooper-Dehoff, J. A. Johnson

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)175-181
Number of pages7
JournalClinical Pharmacology and Therapeutics
Volume96
Issue number2
DOIs
StatePublished - 2014

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Cytochrome P-450 CYP2D6
Metoprolol
Phenotype
Heart Rate
Adrenergic Antagonists
Adrenergic Receptors
Blood Pressure
Hypertension
Enzymes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Hamadeh, I. S., Langaee, T. Y., Dwivedi, R., Garcia, S., Burkley, B. M., Skaar, T., ... Johnson, J. A. (2014). Impact of CYP2D6 polymorphisms on clinical efficacy and tolerability of metoprolol tartrate. Clinical Pharmacology and Therapeutics, 96(2), 175-181. https://doi.org/10.1038/clpt.2014.62

Impact of CYP2D6 polymorphisms on clinical efficacy and tolerability of metoprolol tartrate. / Hamadeh, I. S.; Langaee, T. Y.; Dwivedi, R.; Garcia, S.; Burkley, B. M.; Skaar, Todd; Chapman, A. B.; Gums, J. G.; Turner, S. T.; Gong, Y.; Cooper-Dehoff, R. M.; Johnson, J. A.

In: Clinical Pharmacology and Therapeutics, Vol. 96, No. 2, 2014, p. 175-181.

Research output: Contribution to journalArticle

Hamadeh, IS, Langaee, TY, Dwivedi, R, Garcia, S, Burkley, BM, Skaar, T, Chapman, AB, Gums, JG, Turner, ST, Gong, Y, Cooper-Dehoff, RM & Johnson, JA 2014, 'Impact of CYP2D6 polymorphisms on clinical efficacy and tolerability of metoprolol tartrate', Clinical Pharmacology and Therapeutics, vol. 96, no. 2, pp. 175-181. https://doi.org/10.1038/clpt.2014.62
Hamadeh, I. S. ; Langaee, T. Y. ; Dwivedi, R. ; Garcia, S. ; Burkley, B. M. ; Skaar, Todd ; Chapman, A. B. ; Gums, J. G. ; Turner, S. T. ; Gong, Y. ; Cooper-Dehoff, R. M. ; Johnson, J. A. / Impact of CYP2D6 polymorphisms on clinical efficacy and tolerability of metoprolol tartrate. In: Clinical Pharmacology and Therapeutics. 2014 ; Vol. 96, No. 2. pp. 175-181.
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