[Rationale and methods of the UNAMET study (dose- and CYP2D6-genotype-dependent adverse drug reactions of metoprolol)--a contribution to quality improvement in pharmacotherapy].

Metoprolol has not yet been systematically studied in terms of quality of life and incidence of adverse drug reactions (ADRs). Metoprolol is metabolized by polymorphic CYP2D6, therefore poor CYP2D6 metabolizers may be at higher risk of ADRs. Therefore, it is to be proven whether genotyping is useful to guide initial dose selection. In the ongoing UNAMET study, nonrandomized out-patients start treatment with metoprolol for various disorders. With the use of standard questionnaires, the patients are prospectively evaluated for common ADRs (headache, dizziness, tiredness, sleep disturbances, dyspnea, cold extremities, sexual dysfunction) and quality of life. The questionnaires are filled out before and until 6 weeks after initiating therapy; blood pressure and heart rate are also measured. The acquired data are then related to the patients' metoprolol dose and plasma concentrations, as well as to their metabolic ratio of metoprolol/alpha-OH-metoprolol and CYP2D6 genotype.