From pharmacokinetics to pharmacogenomics: a new approach to tailor immunosuppressive therapy.

One of the main tasks in the management of organ transplantation is the optimization of immunosuppressive therapy, in order to provide therapeutic efficacy limiting drug-related toxicity. In the past years major efforts have been carried out to define therapeutic windows based on blood/plasma levels of each immunosuppressant relating those concentrations to drug dosing and clinical events. Although this traditional approach is able to identify environmental and nongenetic factors that can influence drug exposure during the course of treatment, it presents limitations. Therefore, complementary strategies are advocated. The advent of the genomic era gives birth to pharmacogenomics, a science that studies how the genome as a whole, including single genes as well as gene-to-gene interactions, may affect the action of a drug. This science is of particular importance for drugs characterized by a narrow therapeutic index, such as the immunosuppressants. Preliminary studies focused on polymorphisms of genes encoding for enzymes actively involved in drug metabolism, drug transport and pharmacological target. Pharmacogenomics holds promise for improvement in the ability to individualize immunosuppressive therapy based on the patient's genetic profile, and can be viewed as a support to traditional therapeutic drug monitoring. However, the clinical applicability of this approach is still to be proven.