[Pharmacogenetics or "farm-ecogenetics"?].
Pharmacogenetics and ecogenetics constitute the study of the contribution of genetic factors in interindividual variations in drugs and xenobiotics metabolism respectively and also its physiopathology (toxicity, therapeutic failure and pejorative effect). However, the frontiers between these two fields are interpenetrant with no defined limits. Among the enzymes involved in transformation of drugs/xenobiotics, the cytochrome P450 superfamily plays a major role. Most of the "poor metabolisers" either homozygotes or compound heterozygotes for mutant cytochrome P450 alleles have no detectable enzyme activity. Although phenotyping using a marker drug is usefull, it suffers from several constraints and is influenced by several environmental factors and physiopathological state of the individual. To overcome not only these difficulties but also to improve the overall predictiveness of a drug biotransformation, genotype technology offers an advantage and pharmaco-economic technology further expands the horizon. These fast moving fields must, in near future, allow tailoring of drug prescription on a personalized basis and should, in principle, help in the design and development of novel drug molecules.
Gérard
N
N
INSERM U.458: Pharmacogénétique et Abords Thérapeutiques des Maladies Héréditaires, Hôpital R. Debré, Paris.
Elion
J
J
Krishnamoorthy
R
R
D001711:Biotransformation / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000502:physiology; D003577:Cytochrome P-450 Enzyme System / Q000145:classification / Q000235:genetics / Q000502:physiology; D004342:Drug Hypersensitivity / Q000235:genetics; D064420:Drug-Related Side Effects and Adverse Reactions; D005544:Forecasting; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology; D008862:Microsomes, Liver / Q000201:enzymology; D010597:Pharmacogenetics; D010599:Pharmacokinetics; D010641:Phenotype; D015262:Xenobiotics / Q000493:pharmacokinetics
D007527:Isoenzymes; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D019389:Cytochrome P-450 CYP2D6