title: Relationship between cytochrome P450 polymorphisms and prescribed medication in elderly haemodialysis patients.
abstract: BACKGROUND
  Elderly patients on haemodialysis have a high prevalence of polypharmacy and are at risk of drug-related complications. More than 80 % of all prescribed drugs are metabolized by the cytochrome P450 (CYP) enzyme system. The aims of this study were to describe the prevalence of polymorphism in three CYP isoenzymes and the relationship between CYP polymorphism and prescribed drugs.
  
  
  METHODS
  Fifty-one elderly haemodialysis patients aged ≥65 years were included. CYP-genotyping was carried out in whole blood by a real-time PCR method for detecting common variant alleles in CYP2C9, CYP2C19 and CYP2D6. The allele frequencies were calculated using the Hardy-Weinberg equation.
  
  
  RESULTS
  The overall prevalence of CYP polymorphisms (heterozygous and homozygous) was 77 %. The prevalence of heterozygous carriers of variant alleles coding for defective CYP2D6, CYP2C9 and CYP2C19 was 64, 22 and 55 %, respectively; the prevalence of homozygous carriers was 6 % for each of the CYP2D6, CYP2C9 and CYP2C19 enzymes. The prevalence of the CYP2D6*6, CYP2D6*9 and CYP2D6*41 variant alleles did not differ (p = 0.31) from that in a European Caucasian reference population. Twenty-three patients (45 %) had at least one CYP mutation and used drugs that are metabolized by the CYP isoenzymes. Metoprolol and proton-pump inhibitors were the most commonly used drugs that could be affected by a heterozygous or homozygous mutation.
  
  
  CONCLUSIONS
  Polymorphisms of CYP2C9, CYP2C19 and CYP2D6 are common in elderly haemodialysis patients. Many of these patients have a phenotype with altered CYP enzyme activity and could benefit from close drug monitoring or a drug switch.
authors.affiliation: Medical Division, Department of Nephrology, Akershus University Hospital, 1478 Lørenskog, Norway ; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Krystina
authors.initials: K
authors.lastname: Parker
authors.affiliation: Medical Division, Department of Nephrology, Akershus University Hospital, 1478 Lørenskog, Norway.
authors.forename: Willy
authors.initials: W
authors.lastname: Aasebø
authors.affiliation: Department of Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: Tore
authors.initials: T
authors.lastname: Haslemo
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway ; Medical Division, Department of Pulmonary Medicine, Akershus University Hospital, Lørenskog, Norway ; HØKH, Department of Health Services Research, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Stavem
keywords: Cytochrome P450; Elderly; Haemodialysis; Medication