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Springerplus. 2016 Mar 22;5:350. doi: 10.1186/s40064-016-1986-y. eCollection 2016.

Relationship between cytochrome P450 polymorphisms and prescribed medication in elderly haemodialysis patients.

SpringerPlus

Krystina Parker, Willy Aasebø, Tore Haslemo, Knut Stavem

Affiliations

  1. Medical Division, Department of Nephrology, Akershus University Hospital, 1478 Lørenskog, Norway ; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  2. Medical Division, Department of Nephrology, Akershus University Hospital, 1478 Lørenskog, Norway.
  3. Department of Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
  4. 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.

PMID: 27066364 PMCID: PMC4801827 DOI: 10.1186/s40064-016-1986-y

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.

Keywords: Cytochrome P450; Elderly; Haemodialysis; Medication

References

  1. Clin Pharmacol Ther. 2006 Jan;79(1):103-13 - PubMed
  2. Nagoya J Med Sci. 2011 Feb;73(1-2):25-31 - PubMed
  3. Br J Pharmacol. 2002 Dec;137(7):1039-46 - PubMed
  4. Mol Psychiatry. 2004 May;9(5):442-73 - PubMed
  5. Mol Diagn Ther. 2013 Jun;17 (3):165-84 - PubMed
  6. JAMA. 2002 Apr 3;287(13):1690-8 - PubMed
  7. Thromb J. 2011 Mar 22;9:4 - PubMed
  8. Br J Pharmacol. 2005 Apr;144(8):1067-77 - PubMed
  9. J Clin Psychopharmacol. 2000 Apr;20(2):246-51 - PubMed
  10. Annu Rev Genomics Hum Genet. 2014;15:349-70 - PubMed
  11. J Am Soc Nephrol. 2006 Nov;17(11):3041-8 - PubMed
  12. Am J Hum Genet. 1997 Feb;60(2):284-95 - PubMed
  13. Br J Pharmacol. 2010 Jun;160(4):919-30 - PubMed
  14. Pharmacogenomics. 2002 Mar;3(2):229-43 - PubMed
  15. Br J Pharmacol. 2010 Jun;160(4):907-18 - PubMed
  16. Curr Drug Metab. 2004 Jun;5(3):235-43 - PubMed
  17. Pharmacogenetics. 1999 Dec;9(6):669-82 - PubMed
  18. Pharmacogenetics. 1999 Apr;9(2):217-28 - PubMed
  19. Clin Pharmacol Ther. 2008 Feb;83(2):322-7 - PubMed
  20. Eur J Clin Pharmacol. 2014 Aug;70(8):933-40 - PubMed
  21. Ann Intern Med. 2000 Nov 7;133(9):687-95 - PubMed
  22. Eur J Clin Pharmacol. 2006 Oct;62(10 ):877-80 - PubMed
  23. JAMA. 2010 Oct 27;304(16):1821-30 - PubMed
  24. Hum Mutat. 2003 Dec;22(6):476-85 - PubMed
  25. J Thromb Haemost. 2008 Aug;6(8):1439-41 - PubMed
  26. Clin Transl Med. 2013 Dec 18;2(1):16 - PubMed
  27. N Engl J Med. 2013 Dec 12;369(24):2294-303 - PubMed
  28. Ther Drug Monit. 2012 Feb;34(1):25-30 - PubMed
  29. Expert Opin Drug Metab Toxicol. 2008 Aug;4(8):1065-74 - PubMed
  30. Clin Pharmacol Ther. 2002 Sep;72 (3):333-42 - PubMed
  31. Eur J Clin Pharmacol. 2012 Apr;68(4):363-70 - PubMed
  32. J Thromb Haemost. 2007 Dec;5(12 ):2429-36 - PubMed
  33. Lancet. 1999 Feb 27;353(9154):717-9 - PubMed
  34. Pharmacogenetics. 1997 Jun;7(3):193-202 - PubMed
  35. Clin Pharmacol Ther. 1996 Nov;60(5):522-34 - PubMed
  36. Pharmacogenetics. 1998 Feb;8(1):15-26 - PubMed
  37. JAMA. 2011 Nov 23;306(20):2221-8 - PubMed
  38. Clin Pharmacokinet. 2004;43(4):267-78 - PubMed
  39. Expert Opin Drug Metab Toxicol. 2012 Mar;8(3):371-82 - PubMed
  40. J Pediatr. 2007 Jun;150(6):623-6 - PubMed
  41. Clinics (Sao Paulo). 2009;64(4):273-8 - PubMed
  42. Genet Med. 2005 Feb;7(2):97-104 - PubMed

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