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, 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

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.

Conflict of interest statement

Conflict of Interest:

No conflicts to be disclosed

Figures

Figure 1. Clinical response to metoprolol therapy…
Figure 1. Clinical response to metoprolol therapy by CYP2D6 phenotype
Figure 1A. Comparison of the changes in heart rate (HR) from baseline by CYP2D6 phenotype. The bottom and top of the box represent 25th and 75th percentiles, the band in the middle represent the median (50th percentile), The lower whisker represent the minimum value of the data while the upper whisker represents the maximum value of the data (ANOVA p-value) Figure 1B. Comparison of the changes in systolic blood pressure (SBP) from baseline by CYP2D6 phenotype. The bottom and top of the box represent 25th and 75th percentiles, the band in the middle represent the median (50th percentile), The lower whisker represent the minimum value of the data while the upper whisker represents the maximum value of the data (ANOVA p-value) Figure 1C. Comparison of the changes in diastolic blood pressure (DBP) from baseline by CYP2D6 phenotype. The bottom and top of the box represent 25th and 75th percentiles, the band in the middle represent the median (50th percentile), The lower whisker represent the minimum value of the data while the upper whisker represents the maximum value of the data (ANOVA p-value)

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Source: PubMed

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