title: Cytochrome P450 2D6 phenotype and genotype in hypertensive patients on long-term therapy with metoprolol.
abstract: 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.
  
  
  CONCLUSIONS
  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).
authors.affiliation: Department of Clinical Pharmacology, Faculty of Medicine University of Ostrava and University Hospital Ostrava, Czech Republik. jana.duricova@fno.cz
authors.forename: J
authors.initials: J
authors.lastname: Duricova
authors.forename: I
authors.initials: I
authors.lastname: Perinova
authors.forename: N
authors.initials: N
authors.lastname: Jurckova
authors.forename: I
authors.initials: I
authors.lastname: Jeziskova
authors.forename: I
authors.initials: I
authors.lastname: Kacirova
authors.forename: M
authors.initials: M
authors.lastname: Grundmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008790:Metoprolol / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged; D010641:Phenotype; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D019389:Cytochrome P-450 CYP2D6; D008790:Metoprolol