Cytochrome P450 2D6 phenotype and genotype in hypertensive patients on long-term therapy with metoprolol.

OBJECTIVE: The aim was to compare cytochrome P450 2D6 phenotype and genotype using metoprolol as a probe drug. Further, to investigate the influence of P450 2D6 activity on metoprolol pharmacokinetics and pharmacodynamics in patients on metoprolol therapy. BACKGROUND: Cytochrome P450 2D6 is a highly polymorphic enzyme that contributes to the variability of metoprolol. However, environmental factors also modify drug disposition. METHODS: Forty-nine hypertensive patients were enrolled. Serum metoprolol and α-hydroxymetoprolol concentrations, resting heart rate were measured before, 1, 3 and 4 hours post-dose. RESULTS: Significantly higher normalized metoprolol serum concentrations, normalized metoprolol AUC0-4 and metoprolol oral clearance were observed in patients with lower P450 2D6 metabolic activity. A trend towards a lower resting heart rate before metoprolol intake was also observed in this group of patients. The differences in metoprolol disposition were more expressed when P450 2D6 phenotype instead of genotype was determined. CONCLUSION: Significant variations exist in metoprolol disposition in hypertensive patients. Both genotyping and phenotyping provides a valuable method in determining the enzymatic activity and in optimising metoprolol therapy (Tab. 3, Fig. 8, Ref. 35).

[An effect of continuous and intermittent renal replacement therapy on antibiotic treatment in critically ill patients with sepsis - a practice-based perspective of vancomycin and gentamycin therapies]. / Vliv kontinuální a intermitentní náhrady renálních funkcí na antibiotickou lécbu u kriticky nemocných v sepsi - praktický pohled na lécbu vankomycinem a gentamicinem.

Sepsis and septic shock are common cause of hospitalisation in intensive care unit. Acute kidney injury is an accompanying manifestation of sepsis/septic shock leading to worsening of morbidity and also mortality and requiring use of intermittent or continual renal replacement therapy. Life saving effect is attributed to early and effective antibiotic therapy. Therapeutic drug monitoring and do-sage adjustment is important for successful treatment. Despite therapeutic drug monitoring of both antibiotic agents vankomycin and gentamicin the treatment still rises many questions about the convenient use in septic patients due to their nephrotoxicity.