CYP2D6: Where It All Began

Abstract

This chapter discusses the genetics, metabolic actions, substrates, and inhibitors of cytochrome P450 2D6.

Keywords

Cytochrome P450 CYP2D6 CYP Cytochrome 2D6 Pharmacokinetic Metabolism Metabolic pathway Monoxygenase Liver Intestine Chromosome 22 Phenotype Genotype Phenotypic variability Polymorphism Allele Wild type Heterozygous Homozygous Poor metabolizer Intermediate metabolizer Rapid metabolizer Ultrarapid metabolizer Oxycodone Beta-blockers Dextromethorphan Fluoxetine Codeine Tramadol Prodrug Morphine Antiarrhythmics SSRIs Tricyclic antidepressants Antipsychotics Inhibitors Substrates ritonavir Bupropion Goldenseal Quinidine Hydrocodone Dihydrocodone Ondansetron Celecoxib Diphenhydramine Metoclopramide Ropivacaine Cimetidine Methadone Amiodarone 

References

  1. 1.
    Zhou SF. Polymorphism of human cytochrome P4502D6 and its clinical significance: part 1. Clin Pharmacokinet. 2009;48(11):689–723.PubMedCrossRefGoogle Scholar
  2. 2.
    Kosarac B, Fox AA, Collard CD. Effect of genetic factors on opioid action. Curr Opin Anaesthesiol. 2009;22(4):476–82.PubMedCrossRefGoogle Scholar
  3. 3.
    Sachse C, Brockmöller J, Hildebrand M, et al. Correctness of prediction of the CYP2D6 phenotype confirmed by genotyping 47 intermediate and poor metabolizers of debrisoquine. Pharmacogenetics. 1998;8(2):181–5.PubMedCrossRefGoogle Scholar
  4. 4.
    Shen H, He MM, Liu H, et al. Comparative metabolic capabilities and inhibitory profiles of CYP2D6.1, CYP2D6.10 and CYP2D6.17. Drug Metab Dispos. 2007;35(8):1292–300.PubMedCrossRefGoogle Scholar
  5. 5.
    Stamer UM, Stüber F. Genetic factors in pain and its treatment. Curr Opin Anaesthesiol. 2007;20(5):478–84.PubMedCrossRefGoogle Scholar
  6. 6.
    Sohn DR, Shin SG, Park CW, et al. Metoprolol oxidation polymorphism in a Korean population: comparison with native Japanese and Chinese populations. Br J Clin Pharmacol. 1991;32(4):504–7.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Smith HS. Opioid metabolism. Mayo Clin Proc. 2009;84(7):613–24.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Droll K, Bruce-Mensah K, Otton SV, et al. Comparison of three CYP2D6 probe substrates and genotype in Ghanaians, Chinese and Caucasians. Pharmacogenetics. 1998;8(4):325–33.PubMedCrossRefGoogle Scholar
  9. 9.
    Williams DG, Patel A, Howard RF. Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability. Br J Anaesth. 2002;89(6):839–45.PubMedCrossRefGoogle Scholar
  10. 10.
    Voronov P, Przybylo HJ, Jagannathan N. Apnea in a child after oral codeine: a genetic variant - an ultra-rapid metabolizer. Paediatr Anaesth. 2007;17(7):684–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Madan A, Graham R, Carroll K, et al. Effects of prototypical microsomal enzyme inducers on cytochrome P450 expression in cultured human hepatocytes. Drug Metab Dispos. 2003;31:421–31.PubMedCrossRefGoogle Scholar
  12. 12.
    Candiotti KA, Birnbach DJ, Lubarsky DA, et al. The impact of pharmacogenomics on postoperative nausea and vomiting: do CYP2D6 allele copy number and polymorphisms affect the success or failure of ondansetron prophylaxis? Anesthesiology. 2005;102(3):543–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Janicki PK. Cytochrome P450 2D6 metabolism and 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. Med Sci Monit. 2005;11(10):RA322–8.PubMedGoogle Scholar
  14. 14.
    Wink J, Veering BT, Kruit M, et al. The effect of a long term epidural infusion of ropivacaine on CYP2D6 activity. Anesth Analg. 2008;106(1):143–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Lantz MS, Buchalter EN, Giambanco V. Serotonin syndrome following the administration of tramadol with paroxetine. Int J Geriatr Psychiatry. 1998;13(5):343–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Bartelink IH, Rademaker CM, Schobben AF, et al. Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations. Clin Pharmacokinet. 2006;45(11):1077–97.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • John C. Sanders
    • 1
  • Rachel Koll
    • 2
  • Randal O. Dull
    • 3
  1. 1.Department of AnesthesiologyShriners Hospitals for ChildrenSalt Lake CityUSA
  2. 2.Department of AnesthesiologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  3. 3.Department of AnesthesiologyUniversity of Illinois at ChicagoChicagoUSA

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