Abstract
The aims of this study were to examine the relationships between CYP2D6 genotype and metoprolol dose, S- and R- metoprolol concentrations and clinical effects in patients with systolic heart failure. Data were obtained for 52 subjects, of which 27 had 2 functional alleles (24/27, CYP2D6*1/*1), 22 had 1 functional allele (18/22, CYP2D6*1/*4) and 3 had no functional alleles (CYP2D6*4/*4). Median dose-adjusted concentrations of S- metoprolol (active) were 6.3- and 3.2-fold higher in subjects with zero or one functional allele (P = 0.016 and P = 0.006), respectively, compared with subjects with two functional alleles. For the R- enantiomer (inactive), these concentrations were 10.7- and 3.7-fold higher (P = 0.013 and P = 0.003), respectively. Despite clear gene-concentration differences, no relationships between CYP2D6 genotype and dose or clinical effects could be shown. Although the number with no functional alleles was too small (n = 3) to show effects, in patients with 1 functional allele other sources of variance are likely to be obscuring differences in clinical effects. The Pharmacogenomics Journal (2009) 9, 175-184; doi:10.1038/tpj.2009.9; published online 14 April 2009