Pharmacogenomics

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Pharmacogenomics, or pharmacogenetics, is the "branch of genetics which deals with the genetic variability in individual responses to drugs and drug metabolism (biotransformation)."[1]

Drug toxicity

For more information, see: Drug toxicity.

Among drugs frequently cited in adverse drug reactions, 60% are metabolized by enzymes with genetic variations in metabolism. 7% to 22% of randomly selected have such variation.[2]

Examples include:

Genotyping

Examples are emerging where genotyping may improve drug dosing, although costs are a barrier.[4][5] Other issues in evaluating the role of genotyping have been discussed.[6]

Screening for HLA-B*5701 may reduce the incidence of hypersensitivity reactions to abacavir according to a randomized controlled trial.[7] Six percent of the patients in this study had HLA-B*5701.

Screening for Cytochrome P-450 2C9 polymorphisms may improve warfarin dosing cmopared to the Ageno algorithm[8] or may not improve warfarin dosing compared to the Kovacs 10 mg algorithm[9]. However, even in the latter study a 2.4% absolute reduction in percent out-of-range International Normalized Ratios, although statistically insignificant, occurred.

Drug efficacy

Heart failure and hypertension may be an examples were there are racial variations in responses to drugs. Presumably these variations are due to pharmacogenomics.

References

  1. Anonymous. Pharmacogenetics. National Library of Medicine. Retrieved on 2008-01-22.
  2. Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W (2001). "Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review". JAMA 286 (18): 2270–9. PMID 11710893[e]
  3. The SEARCH Collaborative Group. (2008) SLCO1B1 Variants and Statin-Induced Myopathy. New Eng J Med. PMID 18650507
  4. 4.0 4.1 Anonymous. Table of Valid Genomic Biomarkers in the Context of Approved Drug Labels, Drug Interactions: Table of Substrates, Inhibitors and Inducers. Food and Drug Administration. Retrieved on 2009-01-12.
  5. Lavine G. Jan 15, 2009. HHS panel examines effects of patents, licenses on genetic testing. Am J Health Syst Pharm DOI:10.2146/news090008
  6. Weiss ST, McLeod HL, Flockhart DA, et al (July 2008). "Creating and evaluating genetic tests predictive of drug response". Nat Rev Drug Discov 7 (7): 568–74. DOI:10.1038/nrd2520. PMID 18587383. Research Blogging.
  7. Mallal S, Phillips E, Carosi G, et al (February 2008). "HLA-B*5701 screening for hypersensitivity to abacavir". N. Engl. J. Med. 358 (6): 568–79. DOI:10.1056/NEJMoa0706135. PMID 18256392. Research Blogging.
  8. Caraco Y, Blotnick S, Muszkat M (March 2008). "CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study". Clin. Pharmacol. Ther. 83 (3): 460–70. DOI:10.1038/sj.clpt.6100316. PMID 17851566. Research Blogging.
  9. Anderson JL, Horne BD, Stevens SM, et al (November 2007). "Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation". Circulation 116 (22): 2563–70. DOI:10.1161/CIRCULATIONAHA.107.737312. PMID 17989110. Research Blogging.