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Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.

Brockmöller J, Tzvetkov MV - Eur. J. Clin. Pharmacol. (2008)

Bottom Line: Driven by the advances in molecular biology, pharmacogenetics has evolved within the past 40 years from a niche discipline to a major driving force of clinical pharmacology, and it is currently one of the most actively pursued disciplines in applied biomedical research in general.This has not yet significantly changed common therapeutic practices, but a number of physicians are starting to consider polymorphisms, such as those in CYP2C9, CYP2C19, CYP2D6, TPMT and VKORC1, in daily medical practice.Pharmacogenetics and genomics are becoming substantially integrated fields of the profession of clinical pharmacology, and education in the relevant methods, knowledge and concepts form an indispensable part of the clinical pharmacology curriculum and the professional life of pharmacologists from early drug discovery to pharmacovigilance.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology, Georg August University Göttingen, Göttingen, Germany. jbrockm@gwdg.de

ABSTRACT
Variation in the human genome is a most important cause of variable response to drugs and other xenobiotics. Susceptibility to almost all diseases is determined to some extent by genetic variation. Driven by the advances in molecular biology, pharmacogenetics has evolved within the past 40 years from a niche discipline to a major driving force of clinical pharmacology, and it is currently one of the most actively pursued disciplines in applied biomedical research in general. Nowadays we can assess more than 1,000,000 polymorphisms or the expression of more than 25,000 genes in each participant of a clinical study -- at affordable costs. This has not yet significantly changed common therapeutic practices, but a number of physicians are starting to consider polymorphisms, such as those in CYP2C9, CYP2C19, CYP2D6, TPMT and VKORC1, in daily medical practice. More obviously, pharmacogenetics has changed the practices and requirements in preclinical and clinical drug research; large clinical trials without a pharmacogenomic add-on appear to have become the minority. This review is about how the discipline of pharmacogenetics has evolved from the analysis of single proteins to current approaches involving the broad analyses of the entire genome and of all mRNA species or all metabolites and other approaches aimed at trying to understand the entire biological system. Pharmacogenetics and genomics are becoming substantially integrated fields of the profession of clinical pharmacology, and education in the relevant methods, knowledge and concepts form an indispensable part of the clinical pharmacology curriculum and the professional life of pharmacologists from early drug discovery to pharmacovigilance.

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The pathways of pharmacogenetic and pharmacogenomic research. The routes shown here may not be the only ones, but the figure should illustrate how multiple approaches have to be combined to obtain pharmacogenomic knowledge that is of value for the development of new therapeutics or for the improvement of existing therapies
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Fig6: The pathways of pharmacogenetic and pharmacogenomic research. The routes shown here may not be the only ones, but the figure should illustrate how multiple approaches have to be combined to obtain pharmacogenomic knowledge that is of value for the development of new therapeutics or for the improvement of existing therapies

Mentions: After more than 40 years of pharmacogenetic and pharmacogenomic research, we now have a multitude of options. The highlights of the year 2007 were numerous large genome-wide association studies, and data obtained from some of these studies will result in optimized medical therapies. However, more than before, pharmacogenetics and genomics research remains an iterative process (Fig. 6), and there is much room for opportunities for improvement in each of the approaches. Viewed from the perspective of clinical pharmacologist, research should start with a well-defined and well-designed clinical study and should finally end with improvements for the patients.Fig. 6


Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.

Brockmöller J, Tzvetkov MV - Eur. J. Clin. Pharmacol. (2008)

The pathways of pharmacogenetic and pharmacogenomic research. The routes shown here may not be the only ones, but the figure should illustrate how multiple approaches have to be combined to obtain pharmacogenomic knowledge that is of value for the development of new therapeutics or for the improvement of existing therapies
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2235910&req=5

Fig6: The pathways of pharmacogenetic and pharmacogenomic research. The routes shown here may not be the only ones, but the figure should illustrate how multiple approaches have to be combined to obtain pharmacogenomic knowledge that is of value for the development of new therapeutics or for the improvement of existing therapies
Mentions: After more than 40 years of pharmacogenetic and pharmacogenomic research, we now have a multitude of options. The highlights of the year 2007 were numerous large genome-wide association studies, and data obtained from some of these studies will result in optimized medical therapies. However, more than before, pharmacogenetics and genomics research remains an iterative process (Fig. 6), and there is much room for opportunities for improvement in each of the approaches. Viewed from the perspective of clinical pharmacologist, research should start with a well-defined and well-designed clinical study and should finally end with improvements for the patients.Fig. 6

Bottom Line: Driven by the advances in molecular biology, pharmacogenetics has evolved within the past 40 years from a niche discipline to a major driving force of clinical pharmacology, and it is currently one of the most actively pursued disciplines in applied biomedical research in general.This has not yet significantly changed common therapeutic practices, but a number of physicians are starting to consider polymorphisms, such as those in CYP2C9, CYP2C19, CYP2D6, TPMT and VKORC1, in daily medical practice.Pharmacogenetics and genomics are becoming substantially integrated fields of the profession of clinical pharmacology, and education in the relevant methods, knowledge and concepts form an indispensable part of the clinical pharmacology curriculum and the professional life of pharmacologists from early drug discovery to pharmacovigilance.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology, Georg August University Göttingen, Göttingen, Germany. jbrockm@gwdg.de

ABSTRACT
Variation in the human genome is a most important cause of variable response to drugs and other xenobiotics. Susceptibility to almost all diseases is determined to some extent by genetic variation. Driven by the advances in molecular biology, pharmacogenetics has evolved within the past 40 years from a niche discipline to a major driving force of clinical pharmacology, and it is currently one of the most actively pursued disciplines in applied biomedical research in general. Nowadays we can assess more than 1,000,000 polymorphisms or the expression of more than 25,000 genes in each participant of a clinical study -- at affordable costs. This has not yet significantly changed common therapeutic practices, but a number of physicians are starting to consider polymorphisms, such as those in CYP2C9, CYP2C19, CYP2D6, TPMT and VKORC1, in daily medical practice. More obviously, pharmacogenetics has changed the practices and requirements in preclinical and clinical drug research; large clinical trials without a pharmacogenomic add-on appear to have become the minority. This review is about how the discipline of pharmacogenetics has evolved from the analysis of single proteins to current approaches involving the broad analyses of the entire genome and of all mRNA species or all metabolites and other approaches aimed at trying to understand the entire biological system. Pharmacogenetics and genomics are becoming substantially integrated fields of the profession of clinical pharmacology, and education in the relevant methods, knowledge and concepts form an indispensable part of the clinical pharmacology curriculum and the professional life of pharmacologists from early drug discovery to pharmacovigilance.

Show MeSH