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Published on: December 11, 2016
Pharmacogenomics and individualized drug therapy
Michel Eichelbaum1, Magnus Ingelman-Sundberg, William E Evans
1Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Auerbachstr. 112, D-70376 Stuttgart, Germany. michel.eichelbaum@ikp-stuttgart.de
Annual Review of Medicine
|January 18, 2006
Summary
Pharmacogenetics studies genetic variations affecting drug responses. Understanding these differences, like TPMT and CYP2D6 gene variants, can guide safer and more effective drug therapies.
Area of Science:
- Pharmacogenetics
- Clinical Pharmacology
- Genomics
Background:
- Inherited genetic differences significantly influence individual responses to medications.
- Genetic polymorphisms in drug-metabolizing enzymes affect approximately 30% of all drugs.
- Variations in drug targets also play a crucial role in determining therapeutic outcomes.
Purpose of the Study:
- To highlight the impact of genetic variations on drug efficacy and toxicity.
- To discuss specific examples of pharmacogenetic polymorphisms and their clinical implications.
- To address the limitations hindering the widespread clinical adoption of pharmacogenetic testing.
Main Methods:
- Review of established pharmacogenetic principles and examples.
- Discussion of genetic polymorphisms in drug-metabolizing enzymes (e.g., TPMT, CYP2D6).
- Examination of genetic variations in drug targets influencing drug response.
Main Results:
- Loss of function in thiopurine S-methyltransferase (TPMT) leads to severe toxicity with mercaptopurine/azathioprine.
- CYP2D6 gene duplication is linked to poor antidepressant treatment response.
- Growing evidence supports the influence of genetic polymorphisms on drug response.
Conclusions:
- Pharmacogenetics offers a pathway to personalize drug therapy.
- Clinical implementation is limited by the need for prospective trials demonstrating improved benefit/risk ratios.
- Further research and clinical validation are essential for integrating pharmacogenetics into routine practice.
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