Clinical Pediatric Emergency Medicine
Volume 8, Issue 4 , Pages 262-267 , December 2007

Pharmacogenomics of Analgesic Agents

  • Amy Drendel, DO, MS

      Affiliations

    • Corresponding Author InformationReprint requests and correspondence: Amy Drendel, DO, MS, Pediatric Emergency Medicine, Children's Hospital of Wisconsin, Medical College of Wisconsin, PO Box 1997—Suite C550, Milwaukee, WI 53226.

References 

  1. Motulsky AG. Drug reactions, enzymes and biochemical genetics. JAMA. 1957;165:835–837
  2. Flores CM, Mogil JS. The pharmacogenetics of analgesia: toward a genetically-based approach to pain management. Pharmacogenomics. 2001;2:177–194
  3. Moir MS, Bair E, Shinnick P, et al. Acetaminophen versus acetaminophen with codeine after pediatric tonsillectomy. Laryngoscope. 2000;110:1824–1827
  4. St Charles CS, Matt BH, Hamilton MM, et al. A comparison of ibuprofen versus acetaminophen with codeine in the young tonsillectomy patient. Otolaryngol Head Neck Surg. 1997;117:76–82
  5. Clark E, Plint AC, Correll R, et al. A randomized, controlled trial of acetaminophen, ibuprofen, and codeine for acute pain relief in children with musculoskeletal trauma. Pediatrics. 2007;119:460–467
  6. Eckhardt K, Li S, Ammon S, et al. Same incidence of adverse drug events after codeine administration irrespective of the genetically determined differences in morphine formation. Pain. 1998;76:27–33
  7. Lotsch J, Skarke C, Schmidt H, et al. Evidence for morphine-independent central nervous opioid effects after administration of codeine: contribution of other codeine metabolites. Clin Pharmacol Ther. 2006;79:35–48
  8. Sim S, Ingelman-Sundberg M, Daly AK, et al. Home page of the human cytochrome P450 (CYP) allele nomenclature committee. Available at: http://www.cypalleles.ki.se/[Accessed July 21, 2007].
  9. Bernard S, Neville KA, Nguyen AT, et al. Interethnic differences in genetic polymorphisms of CYP2D6 in the US population: clinical implications. Oncologist. 2006;11:126–135
  10. Findlay JW, Jones EC, Burtz RF, et al. Plasma codeine and morphine concentrations after therapeutic oral doses of codeine containing analgesia. Clin Pharmacol Ther. 1978;24:60–68
  11. Sindrup SH, Brosen K, Bjerring P, et al. Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine. Clin Pharmacol Ther. 1990;48:686–693
  12. Dayer P, Desmeules J, Leemann T, et al. Bioactivation of the narcotic drug codeine in human liver is mediated by the polymorphic monooxygenase catalyzing debrisoquine 4-hydroxylation. Biochem Biophys Res Commun. 1988;152:411–416
  13. Yue QY, Svensson JO, Alm C, et al. Codeine O-demethylation co-segregates with polymorphic debrisoquine hydroxylation. Br J Clin Pharmacol. 1989;28:639–645
  14. Chen ZR, Somogyi AA, Bochner F. Polymorphic O-demethylation of codeine. Lancet. 1988;2:914–915
  15. Chen ZR, Somogyi AA, Reynolds G, et al. Disposition and metabolism of codeine after single and chronic doses in one poor and seven extensive metabolisers. Br J Clin Pharmacol. 1991;31:381–390
  16. Persson K, Sjostrom S, Sigurdardottir I, et al. Patient-controlled analgesia (PCA) with codeine for postoperative pain relief in ten extensive metabolisers and one poor metaboliser of dextromethorphan. Br J Clin Pharmacol. 1995;39:182–186
  17. Poulsen L, Riishede L, Brosen K, et al. Codeine in post-operative pain. Study of the influence of sparteine phenotype and serum concentrations of morphine and morphine-6-glucuronide. Eur J Clin Pharmacol. 1998;54:451–454
  18. Treluyer JM, Jacqz-Aigrain E, Alvarez F, et al. Expression of CYP2D6 in developing human liver. Eur J Biochem. 1991;202:583–588
  19. Blake MJ, Gaedigk A, Pearce RE, et al. Ontogeny of dextromethorphan O- and N-demethylation in the first year of life. Clin Pharmacol Ther. 2007;81:510–516
  20. 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;89:839–845
  21. Hutchinson MR, Menelaou A, Foster DJ, et al. CYP2D6 and CYP3A4 involvement in the primary oxidative metabolism of hydrocodone by human liver microsomes. Br J Clin Pharmacol. 2004;57:287–297
  22. Otton SV, Schadel M, Cheung SW, et al. CYP2D6 phenotype determines the metabolic conversion of hydrocodone to hydromorphone. Clin Pharmacol Ther. 1993;54:463–472
  23. Lalovic B, Kharasch E, Hoffer C, et al. Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: role of circulating active metabolites. Clin Pharmacol Ther. 2006;79:461–479
  24. Rasmussen I. Identification of cytochrome P450 isoforms involved in the metabolism of oxycodone. Master of Science Thesis, University of Adelaide, Adelaide, 2000. p. 141.
  25. Lalovic B, Phillips B, Risler LL, et al. Quantitative contribution of CYP2D6 and CYP3A to oxycodone metabolism in human liver and intestinal microsomes. Drug Metab Disp. 2004;32:447–454
  26. Heiskanen T, Olkkola KT, Kalso E. Effects of blocking CYP2D6 on the pharmacokinetics and pharmacodynamics of oxycodone. Clin Pharmacol Ther. 1998;64:603–611
  27. Maddocks I, Somogyi A, Abbott F, et al. Attenuation of morphine-induced delirium in palliative care by substitution with infusion of oxycodone. J Pain Symptom Manage. 1996;12:182–189
  28. Caraco Y, Sheller J, Wood AJ. Pharmacogenetic determination of the effects of codeine and prediction of drug interactions. J Pharmacol Exp Ther. 1996;278:1165–1174
  29. Mikus G, Trausch B, Rodewald C, et al. Effect of codeine on gastrointestinal motility in relation to CYP2D6 phenotype. Clin Pharmacol Ther. 1997;61:459–466
  30. Hasselstrom J, Yue QY, Sawe J. The effect of codeine on gastrointestinal transit in extensive and poor metabolisers of debrisoquine. Eur J Clin Pharmacol. 1997;53:145–148
  31. Lotsch J, Skarke C, Liefhold J, et al. Genetic predictors of the clinical response to opioid analgesics: clinical utility and future perspectives. Clin Pharm. 2004;43:983–1013
  32. Ikeda K, Ide S, Han W, et al. How individual sensitivity to opiates can be predicted by gene analyses. Trends Pharmacol Sci. 2005;26:311–317
  33. Somogyi AA, Barratt DT, Coller JK. Pharmacogenetics of opioids. Clin Pharmacol Ther. 2007;81:429–444
  34. Schwarz UI. Clinical relevance of genetic polymorphisms in the human CYP2C9 gene. Eur J Clin Invest. 2003;33:23–30
  35. Kirchheiner J, Meineke I, Freytag G, et al. Enantiospecific effects of cytochrome P450 2C9 amino acid variants on ibuprofen pharmacokinetics and on the inhibition of cyclooxygenases 1 and 2. Clin Pharmacol Ther. 2002;72:62–75

PII: S1522-8401(07)00054-7

doi: 10.1016/j.cpem.2007.08.001

Clinical Pediatric Emergency Medicine
Volume 8, Issue 4 , Pages 262-267 , December 2007

Article Tools