Pharmacogenetic aspects of current pharmacotherapy
Authors:
Ondřej Slanař 1,2; Tomáš Zima 2
Authors‘ workplace:
Univerzita Karlova v Praze, 1. lékařská fakulta, Farmakologický ústav
1; Univerzita Karlova v Praze, 1. lékařská fakulta, Ústav klinické biochemie a laboratorní diagnostiky
2
Published in:
Čas. Lék. čes. 2010; 149: 472-475
Category:
Review Article
Overview
Pharmacogenetics is a specific area of personalized medicine. Pharmacogenetic testing is in the ideal situation conducted prior to the initiation of pharmacotherapy in order to increase efficacy or to minimize risk of toxicity in predisposed patients. There are only few examples of such prospective pharmacogenetics in real praxis so far. We summarize examples of pharmacogenetic tests used in praxis. The pharmacogenetic testing should be applied whenever there is evidence that such test can bring benefit over the therapy without such guidance. However, for most of the drugs on the market, reliable evidence is missing and it will take a lot of effort to obtain pharmacogenetic data for future wider use of these tests.
Key words:
pharmacogenetics, personalized medicine, individualized treatment.
Sources
1. Cascorbi I. The promises of personalized medicine. Eur J Clin Pharmacol 2010; 66(8): 749–754.
2. Mallal S, Phillips E, Carosi G, et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 2008; 358(6): 568–579.
3. Slanar O, Bortlik M, Buzkova H, et al. Polymorphisms of the TPMT gene in the Czech healthy population and patients with inflammatory bowel disease. Nucleosides Nucleotides Nucleic Acids 2008; 27(6): 835–838.
4. Slanar O, Chalupna P, Novotny A, et al. Fatal myelotoxicity after azathioprine treatment. Nucleosides Nucleotides Nucleic Acids 2008; 27(6): 661–665.
5. Zhou S. Clinical pharmacogenomics of thiopurine S‑methyltransferase. Curr Clin Pharmacol 2006; 1(1): 119–128.
6. Caraco Y, Blotnick S, Muszkat M. CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study. Clin Pharmacol Ther 2008; 83(3): 460–470.
7. D‘Andrea G, D‘Ambrosio RL, Di Perna P, et al. A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood 2005; 105(2): 645–649.
8. Klein TE, Altman RB, Eriksson N, et al. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med 2009; 360(8): 753–764.
9. Ho PM, Maddox M, Wang L, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009; 301(9): 937–944.
10. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 2009; 360(4): 354–362.
11. Higgins MJ, Stearns V. CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep 12(1): 7–15.
12. Laika B, Leucht S, Heres S, et al. Intermediate metabolizer: increased side effects in psychoactive drug therapy. The key to cost-effectiveness of pretreatment CYP2D6 screening? Pharmacogenomics J 2009; 9(6): 395–403.
13. Sjoqvist F, Eliasson E. The convergence of conventional therapeutic drug monitoring and pharmacogenetic testing in personalized medicine: focus on antidepressants. Clin Pharmacol Ther 2007; 81(6): 899–902.
14. Zackrisson AL, Lindblom B, Ahlner J. High Frequency of Occurrence of CYP2D6 Gene Duplication/Multiduplication Indicating Ultrarapid Metabolism Among Suicide Cases. Clin Pharmacol Ther 2010; in press.
15. Kirchheiner J, Brosen K, Dahl ML, et al. CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages. Acta Psychiatr Scand 2001; 104(3): 173–192.
16. Seeringer A, Kirchheiner J. Pharmacogenetics-guided dose modifications of antidepressants. Clin Lab Med 2008; 28(4): 619–626.
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Journal of Czech Physicians
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