Tests pharmacogénétiques : leur place en pratique médicale courante et dans le développement des médicaments

Abstract

Pharmacogenetic tests can identify the role of genetic factors in the inter-individual variability of drug responsiveness. This variability can involve three systems, namely drug-metabolizing enzymes, transmembrane drug transporters, and drug effctor sites (receptors, enzymes, ion, channels, etc.). At present, pharmacogenetic testing is rarely used in clinical practice. A rapid survey of the four laboratories conducting such tests for Paris hospitals shows that about 750 tests were done during a 12-months period in 2004-2005, and that most focused on allelic variants of drug-metabolizing enzymes. Three other European laboratories perform between 25, and 7.000 tests per year. However, the number of pharmacogenetic tests is set to grow rapidely in the near future. The role of genetic factors in adverse drug reactions (ADR) has not yet been the subject of a systematic study. Drug-drug interactions that inhibit or induce certain enzyme activities are a major cause of adverse reactions, but they have not been exhaustively studied Pharmacogenetic and pharmacogenomic tools are increasingly used in the drug development process. This should result in the discovery of new therapeutic targets and in a better understanding of factors governing drug efficacy and tolerability. DNA samples are already collected systematically in many phase II and III clinical trials, and registration agencies such as the FDA are establishing guidelines for the submission of pharmacogenetic data on new drugs. These efforts, together with DNA samples collection during post-registration pharmacoepidemiological studies, should help to understand inter-individual variability in drug efficacy and tolerability. They may also result in the identification of new drug targets and will help to tailor therapy to the individual patient.