title: Variation in the CYP2D6 genotype is not associated with carvedilol dose changes in patients with heart failure.
abstract: OBJECTIVE
  Carvedilol is the standard of care for heart failure (HF) patients. Carvedilol is partially metabolized by the highly polymorphic enzyme, CYP2D6. To reach an effective dose while avoiding adverse drug reactions (ADRs), testing of CYP2D6 genotype prior to carvedilol initiation may be considered. The objectives of this study were to determine CYP2D6 metabolic genotypes in an Israeli cohort of HF patients and to investigate the relationship between genotype, carvedilol dose and number of ADRs to determine the importance of CYP2D6 genotyping prior to treatment initiation.
  
  
  METHODS
  Ninety-three patients with HF on carvedilol were CYP2D6 genotyped and classified as poor (PM), intermediate (IM), extensive (EM) or ultrarapid (UM) metabolizers. Carvedilol dose and ADRs were calculated and correlated with genotype using linear regression statistic analysis.
  
  
  CONCLUSIONS
  The distribution of the CYP2D6 phenotype in the Israeli population with HF is similar to the European general population. There were no significant differences of carvedilol dose and number of ADRs among genotype groups. Genotype group affiliation and number of adverse drug reactions were not predictive of carvedilol dose changes.
  
  
  CONCLUSIONS
  Genotype group affiliation and number of adverse drug reactions were not predictive of carvedilol dose during therapy for patients with HF. The Israeli CYP2D6 phenotype distribution in HF patients was consistent with the frequency in the general European population.
authors.affiliation: Clinical Pharmacology Unit, Kaplan Medical Center, Hebrew University and Hadassah Medical School, Rehovot, Jerusalem, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Shihmanter
authors.forename: I
authors.initials: I
authors.lastname: Nulman
authors.forename: S
authors.initials: S
authors.lastname: Goland
authors.forename: A
authors.initials: A
authors.lastname: Caspi
authors.forename: A
authors.initials: A
authors.lastname: Bar-Haim
authors.forename: I
authors.initials: I
authors.lastname: Harary
authors.forename: M
authors.initials: M
authors.lastname: Berkovitch
authors.forename: L
authors.initials: L
authors.lastname: Arcavi
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000368:Aged; D002227:Carbazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000077261:Carvedilol; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007557:Israel; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011412:Propanolamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D019389:Cytochrome P-450 CYP2D6
keywords: CYP2D6; adverse drug reactions; carvedilol; heart failure