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; T. C. Skaar; A. B. Chapman; J. G. Gums; S. T. Turner; Y. Gong; R. M. Cooper-Dehoff; J. A. Johnson

doi:10.1038/clpt.2014.62

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, T. C. Skaar, A. B. Chapman, J. G. Gums, S. T. Turner, Y. Gong, R. M. Cooper-Dehoff, J. A. Johnson

Nephrology and Hypertension

Research output: Contribution to journal › Article › peer-review

53 Scopus citations

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 language	English (US)
Pages (from-to)	175-181
Number of pages	7
Journal	Clinical pharmacology and therapeutics
Volume	96
Issue number	2
DOIs	https://doi.org/10.1038/clpt.2014.62
State	Published - 2014

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)

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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. (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

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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.",

author = "Hamadeh, {I. S.} and Langaee, {T. Y.} and R. Dwivedi and S. Garcia and Burkley, {B. M.} and Skaar, {T. C.} and Chapman, {A. B.} and Gums, {J. G.} and Turner, {S. T.} and Y. Gong and Cooper-Dehoff, {R. M.} and Johnson, {J. A.}",

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AU - Burkley, B. M.

AU - Skaar, T. C.

AU - Chapman, A. B.

AU - Gums, J. G.

AU - Turner, S. T.

AU - Gong, Y.

AU - Cooper-Dehoff, R. M.

AU - Johnson, J. A.

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

Abstract

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