[Contribution of genotyping and phenotyping of biotransformation in therapeutic drug monitoring].
Genetic-controlled biotransformation is a factor partly accounting for interindividual variability in drug responses. This control occurs via gene coding for polymorphic enzymes or rare genetic variants. Currently, the clinical relevance of genetically controlled biotransformation concerns only a few drugs. Determinants of clinical relevance depend on the size of the contribution of the metabolic pathway subject to genetic control, the existence of a relationship between the concentration and the therapeutic and/or toxic effect, a low therapeutic index and a pharmacokinetic variability smaller than pharmacodynamic one. Phenotyping using test drugs allows the determination of the activity of the drug-metabolizing enzyme but can be hampered by drug-drug interactions and some pathophysiological states. Genotyping can offer additional information such as the differentiation between ultra rapid metabolizers and patients who comply poorly with drug treatment, and the differentiation between genetic and environmental determinants. Genotyping and phenotyping can help predict dosage requirements. Currently the number of clinical laboratories using these tools in the drug-monitoring approach is small.
Barré
J
J
Laboratoire de Pharmacologie et Toxicologie, Centre Hospitalier Intercommunal, 40, Avenue de Verdun, 94010 Creteil, France.
D001711:Biotransformation / Q000235:genetics*; D016903:Drug Monitoring; D004798:Enzymes / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D010641:Phenotype; D011110:Polymorphism, Genetic
D004798:Enzymes