title: The relationship between plasma concentration of metoprolol and CYP2D6 genotype in patients with ischemic heart disease.
abstract: BACKGROUND
  Metoprolol is the one of the most commonly used β-blockers in the treatment of ischemic heart disease and it is extensively metabolized in the liver undergoing oxidation by CYP2D6 isoenzyme of cytochrome P450. Gene encoding the CYP2D6 enzyme is characterized by genetic polymorphism. The CYP2D6 oxidation polymorphism has a major impact on the effectiveness and safety of the treatment. The aim of the study was to evaluate the relationship between plasma concentration of metoprolol and the CYP2D6 genotype in patients with ischemic heart disease.
  
  
  METHODS
  Fifty patients were interviewed and subsequently enrolled into the study. The patients received metoprolol twice daily at a dose of 50mg. The blood samples were analyzed for two major defective alleles for CYP2D6 - CYP2D6*4 and CYP2D6*3--by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Metoprolol concentration in plasma was determined by using the new and unique high-performance liquid chromatography (HPLC) method in the author's own modification with Corona CAD detector (Charged Aerosol Detection).
  
  
  RESULTS
  In the test group, genotypes conditioning poor oxidation (PM) occurred in 3 patients (6%), while 47 patients (94%) had genotypes coding for extensive metabolism (EM). Patients with PM genotypes had significantly higher plasma concentrations of metoprolol than the patients with EM genotype (mean 92.25 ± SD 36.78 ng/ml vs. mean 168.22 ± SD 5.61 ng/ml, respectively). Established relationships were statistically significant (NIR test, p=0.0009).
  
  
  CONCLUSIONS
  This study demonstrated that the CYP2D6 genotype remains a major determinant of the metoprolol plasma concentrations. The pharmacogenetic effect is likely to have consequences on both, the clinical benefit of metoprolol treatment and adverse drug reactions. The use of Corona CAD detector seems to be a very good alternative method for the determination of metoprolol concentration in plasma.
authors.affiliation: Department of Pharmacogenetics, Medical University of Lodz, Łódź, Poland. Electronic address: anna.wojtczak@umed.lodz.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Wojtczak
authors.affiliation: Institute of Chemical Technology of Food, Lodz University of Technology, Łódź, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Wojtczak
authors.affiliation: Department of Pharmacogenetics, Medical University of Lodz, Łódź, Poland.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Skrętkowicz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000097:blood*; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics
chemical_list: D019389:Cytochrome P-450 CYP2D6; D008790:Metoprolol
keywords: CYP2D6 genotype; Metoprolol