[Xenobiotic-metabolizing polymorphic enzymes. An opportunity for individualized drug treatment].
Interindividual variability in drug responses can complicate patient management. This variability is partly due to genetic factors that affect pharmacokinetic and pharmacodynamic behavior Pharmacogenetics is a discipline focusing on the molecular mechanisms underlying drug responses. Its overriding goal is to optimize drug treatments, in terms of both their efficacy and their safety. Polymorphisms of genes that encode drug-metabolizing enzymes, transporter molecules and receptors have a well-documented impact on the distribution and effects of many medications. This review examines the scope of pharmacogenetics, the molecular bases of interindividual variations in drug responses, and the methods used to assess the individual risk of drug failure or toxicity. Pharmacogenetic approaches have already entered the clinical arena, resulting in significant improvements in patient management. Clinical validation of new pharmacogenetic tests and the development of new efficient genotyping technologies should rapidly lead to patient-tailored therapy.
Lhermitte
Michel
M
EA 2679, Université de Lille 2 et Service de Toxicologie et Gènopathies, CHRU de Lille. Avenue du Pr. J. Leclercq, 59037 Lille Cedex.
Allorge
Delphine
D
Broly
Franck
F
D000123:Acetyltransferases / Q000502:physiology; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000502:physiology; D004358:Drug Therapy / Q000592:standards*; D005838:Genotype; D006801:Humans; D015122:Mercaptopurine / Q000378:metabolism; D008780:Methyltransferases / Q000502:physiology; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011619:Psychotropic Drugs / Q000378:metabolism; D013866:Thioguanine / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism
D004364:Pharmaceutical Preparations; D011619:Psychotropic Drugs; D015262:Xenobiotics; D015122:Mercaptopurine; D019389:Cytochrome P-450 CYP2D6; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D000123:Acetyltransferases; D013866:Thioguanine