Pharmacogenomics
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
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:
- The SLCO1B1 Variants and statin-induced myopathy[3]
- Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) patients with HLA-B*1502 allele who take carbamazepine[4].
Genotyping
Screening for HLA-B*5701 may reduce the incidence of hypersensitivity reactions to abacavir according to a randomized controlled trial.[5] 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[6] or may not improve warfarin dosing compared to the Kovacs 10 mg algorithm[7].
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
- ↑ Anonymous. Pharmacogenetics. National Library of Medicine. Retrieved on 2008-01-22.
- ↑ 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]
- ↑ The SEARCH Collaborative Group. (2008) SLCO1B1 Variants and Statin-Induced Myopathy. New Eng J Med. PMID 18650507
- ↑ Anonymous. Table of Valid Genomic Biomarkers in the Context of Approved Drug Labels. U.S. Food and Drug Administration
- ↑ 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.
- ↑ 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.
- ↑ 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.
External links
- http://www.pharmgkb.org/ - Pharmacogenetics Research Network and Database (Standford University)
- http://medicine.iupui.edu/flockhart/ - Cytochrome P450 interactions (Indiana University Department of Medicine)
- http://www.fda.gov/cder/genomics/genomic_biomarkers_table.htm - Table of Valid Genomic Biomarkers in the Context of Approved Drug Labels. U.S. Food and Drug Administration.