Clinical utility of pharmacogenetics for predicting drug efficacy and toxicity

Abstract

The narrow therapeutic index of most pharmaceutical agents and the severe consequences of undertreatment or overdosing have led to search for molecular predictive factors of toxicity and efficacy. Genetic factors involved in drug metabolism and transport partly explain inter-individual variability in drug response. Pharmacogenetics focuses on the molecular mechanisms involved in drug response. Its ultimate goal is to optimize the treatments, combining the better efficacy with the minimal risk of severe side-effects. Polymorphisms in genes encoding specific drugmetabolising enzymes may be encountered in some individuals and allow characterizing different groups in the general population as low, rapid and even ultra-rapid metabolisers. Phenotyping and genotyping tests are now available to determine or predict the metabolic status of an individual and, thus, enabling to evaluate the risk of drug failure or toxicity. Several clinical applications of pharmacogenetics (thiopurines, antivitamine K, codeine, and tramadol) have already been developed in the routine medical practice 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 should further promote pharmacogenetics in clinical practice and lead to the development of a patient-tailored drug therapy.