From evidence based medicine to mechanism based medicine. Reviewing the role of pharmacogenetics
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Aim of the review The translation of evidence based medicine to a specific patient presents a considerable challenge. We present by means of the examples nortriptyline, tramadol, clopidogrel, coumarins, abacavir and antipsychotics the discrepancy between available pharmacogenetic information and its implementation in daily clinical practice. Method Literature review. Results A mechanism based approach may be helpful to personalize medicine for the individual patient to which pharmacogenetics may contribute significantly. The lack of consistency in what we accept in bioequivalence and in pharmacogenetics of drug metabolising enzymes is discussed and illustrated with the example of nortriptyline. The impact of pharmacogenetics on examples like tramadol, clopidogrel, coumarins and abacavir is described. Also the present status of the polymorphisms of 5-HT2A and C receptors in antipsychotic-induced weight gain is presented as a pharmacodynamic example with until now a greater distance to clinical implementation. Conclusion The contribution of pharmacogenetics to tailor-made pharmacotherapy, which especially might be of value for patients deviating from the average, has not yet reached the position it seems to deserve.
KeywordsDrug metabolising enzymes Mechanism based medicine Pharmacodynamics Pharmacogenetics Pharmacokinetics
Conflicts of interest
The division of Pharmacoepidemiology & Clinical Pharmacology employing author Anke-Hilse Maitland-van der Zee, has received unrestricted funding for pharmacoepidemiological research from GlaxoSmithKline, Novo Nordisk, the private–public funded Top Institute Pharma (http://www.tipharma.nl, includes co-funding from universities, government, and industry), the Dutch Medicines Evaluation Board, and the Dutch Ministry of Health.
This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
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