Impact of the CYP2D6 Genotype on the Clinical Effects of Metoprolol: A Prospective Longitudinal Study

After administration of metoprolol, plasma concentrations of the drug are markedly higher in CYP2D6 poor metabolizers (PMs) than in non‐PMs. In a prospective double‐blind 3‐month study, we investigated whether this translates into differences in metoprolol's effects after initiation of therapy. Despite administering equal doses to PMs and non‐PMs, metoprolol plasma concentrations were 4.9‐fold higher in the PM group. Metoprolol evoked significantly and persistently greater reductions in heart rate, diastolic blood pressure, and mean arterial pressure in PMs than in non‐PMs. It appears, therefore, that the CYP2D6 genotype contributes to interindividual differences in metoprolol response. Clinical Pharmacology & Therapeutics (2009); 85, 3, 269–272 doi:10.1038/clpt.2008.218