Therapeutic drug monitoring in clinical practice and research

Introduction: The human cytochrome P450 2D6 (CYP2D6) is involved in the oxidative metabolism of about 25 % of all commonly prescribed drugs. It is characterized by high range of interindividual variability due to both environmental and genetic factors. The ability to measure the activity of CYP2D6 enzyme is of high significance. Genotyping alone is not sufficient to accurately predict an individual's actual CYP2D6 activity, phenotyping on the other hand can determine the exact enzymatic activity as it also reflects non-genetic factors. Beta-blocker agent metoprolol undergoes extensive pre-systemic elimination, with enzyme CYP2D6 accounting for about 70 to 80 % of its metabolism. Metoprolol also serves as one of the probe drugs of CYP2D6. The metabolic ratio of metoprolol over its metabolite -hydroxymetoprolol in plasma 3 hours after metoprolol administration is used for the measurement of CYP2D6 enzyme activity. Aims: To compare CYP2D6 metabolic activity after first metoprolol dose and in steady state. Further to investigate the influence of CYP2D6 activity on metoprolol pharmacokinetics and pharmacodynamics in patients on metoprolol therapy. Methods: Thirteen adult hypertensive patients in whom an introduction of beta-blocker metoprolol was indicated were included for comparison of CYP2D6..