[Pharmacogenetics or the promise of a personalized medicine: variability in drug metabolism and transport].
There is much variability in the manner individuals respond to drugs, such that the management of some drugs is problematic. In France, the incidence of hospital admissions related to adverse drug reactions is estimated to be 3.2 %, at an annual cost of over 300 millions euros. Genetic factors affecting the pharmacokinetics and pharmacodynamics of drugs partly explain interindividual variability in drug response. Pharmacogenetic focuses on the molecular mechanisms involved in drug response, and its ultimate goal is the optimisation of drug treatments, both in terms of efficacy and safety. Numerous polymorphisms in genes encoding drug-metabolising enzymes, transporters and receptors have been described and their consequences on disposition and effect of a substantial number of medications have been elucidated. This review focuses on variability of drug metabolism and transport to define the objectives of pharmacogenetics, the molecular bases of interindividual variation in drug response and the methods used for the evaluation of the individual risk of drug failure or toxicity. Some clinical applications of pharmacogenetics have already been developed in routine medicine resulting in significant improvement in patient treatment. The clinical validation of an increasing number of pharmacogenetic tests, as well as the development of new highly efficient technologies for genotyping (real-time PCR, DNA chips) should further promote pharmacogenetics in clinical practice and lead to the development of a patient-tailored drug therapy.
Allorge
D
D
Laboratoire de biochimie et de biologie moléculaire, Hôpital Calmette, CHRU de Lille et EA2679, Faculté de médecine / pôle recherche, Lille. dallorge@univ-lille2.fr
Loriot
M-A
MA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000925:Anticoagulants / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000502:physiology; D005838:Genotype; D006801:Humans; D008780:Methyltransferases / Q000502:physiology; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D011619:Psychotropic Drugs / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000925:Anticoagulants; D000970:Antineoplastic Agents; D004364:Pharmaceutical Preparations; D011619:Psychotropic Drugs; D019389:Cytochrome P-450 CYP2D6; D008780:Methyltransferases; C022745:thiopurine methyltransferase